Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8+ T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness.
Identifieur interne : 000291 ( Main/Exploration ); précédent : 000290; suivant : 000292Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8+ T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness.
Auteurs : Jingxia Wu [Allemagne] ; Sicong Ma [Allemagne] ; Roger Sandhoff [Allemagne] ; Yanan Ming [Allemagne] ; Agnes Hotz-Wagenblatt [Allemagne] ; Vincent Timmerman [Belgique] ; Nathalie Bonello-Palot [France] ; Beate Schlotter-Weigel [Allemagne] ; Michaela Auer-Grumbach [Autriche] ; Pavel Seeman [République tchèque] ; Wolfgang N. Löscher [Autriche] ; Markus Reindl [Autriche] ; Florian Weiss [Allemagne] ; Eric Mah [États-Unis] ; Nina Weisshaar [Allemagne] ; Alaa Madi [Allemagne] ; Kerstin Mohr [Allemagne] ; Tilo Schlimbach [Allemagne] ; Rubí M-H Velasco Cárdenas [Allemagne] ; Jonas Koeppel [Allemagne] ; Florian Grünschl Ger [Allemagne] ; Lisann Müller [Allemagne] ; Maren Baumeister [Allemagne] ; Britta Brügger [Allemagne] ; Michael Schmitt [Allemagne] ; Guido Wabnitz [Allemagne] ; Yvonne Samstag [Allemagne] ; Guoliang Cui [Allemagne]Source :
- Immunity [ 1097-4180 ] ; 2019.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen (MeSH), Animaux (MeSH), Cellules cultivées (MeSH), Chorioméningite lymphocytaire (immunologie), Chorioméningite lymphocytaire (virologie), Complexe-1 cible mécanistique de la rapamycine (métabolisme), Cytokines (biosynthèse), Femelle (MeSH), Humains (MeSH), Lymphocytes T CD8+ (immunologie), Mâle (MeSH), Neuropathies héréditaires sensitives et autonomes (génétique), Prolifération cellulaire (MeSH), Serine C-palmitoyltransferase (génétique), Souris (MeSH), Souris de lignée C57BL (MeSH), Sphingolipides (biosynthèse), Stress du réticulum endoplasmique (génétique), Stress du réticulum endoplasmique (immunologie), Transduction du signal (immunologie), Virus de la chorioméningite lymphocytaire (immunologie).
- MESH :
- biosynthèse : Cytokines, Sphingolipides.
- génétique : Neuropathies héréditaires sensitives et autonomes, Serine C-palmitoyltransferase, Stress du réticulum endoplasmique.
- immunologie : Chorioméningite lymphocytaire, Lymphocytes T CD8+, Stress du réticulum endoplasmique, Transduction du signal, Virus de la chorioméningite lymphocytaire.
- métabolisme : Complexe-1 cible mécanistique de la rapamycine.
- virologie : Chorioméningite lymphocytaire.
- Adulte d'âge moyen, Animaux, Cellules cultivées, Femelle, Humains, Mâle, Prolifération cellulaire, Souris, Souris de lignée C57BL.
English descriptors
- KwdEn :
- Animals (MeSH), CD8-Positive T-Lymphocytes (immunology), Cell Proliferation (MeSH), Cells, Cultured (MeSH), Cytokines (biosynthesis), Endoplasmic Reticulum Stress (genetics), Endoplasmic Reticulum Stress (immunology), Female (MeSH), Hereditary Sensory and Autonomic Neuropathies (genetics), Humans (MeSH), Lymphocytic Choriomeningitis (immunology), Lymphocytic Choriomeningitis (virology), Lymphocytic choriomeningitis virus (immunology), Male (MeSH), Mechanistic Target of Rapamycin Complex 1 (metabolism), Mice (MeSH), Mice, Inbred C57BL (MeSH), Middle Aged (MeSH), Serine C-Palmitoyltransferase (genetics), Signal Transduction (immunology), Sphingolipids (biosynthesis).
- MESH :
- chemical , biosynthesis : Cytokines, Sphingolipids.
- genetics : Endoplasmic Reticulum Stress, Hereditary Sensory and Autonomic Neuropathies, Serine C-Palmitoyltransferase.
- immunology : CD8-Positive T-Lymphocytes, Endoplasmic Reticulum Stress, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Signal Transduction.
- chemical , metabolism : Mechanistic Target of Rapamycin Complex 1.
- virology : Lymphocytic Choriomeningitis.
- Animals, Cell Proliferation, Cells, Cultured, Female, Humans, Male, Mice, Mice, Inbred C57BL, Middle Aged.
Abstract
Patients with the neurological disorder HSAN-I suffer frequent infections, attributed to a lack of pain sensation and failure to seek care for minor injuries. Whether protective CD8+ T cells are affected in HSAN-I patients remains unknown. Here, we report that HSAN-I-associated mutations in serine palmitoyltransferase subunit SPTLC2 dampened human T cell responses. Antigen stimulation and inflammation induced SPTLC2 expression, and murine T-cell-specific ablation of Sptlc2 impaired antiviral-T-cell expansion and effector function. Sptlc2 deficiency reduced sphingolipid biosynthetic flux and led to prolonged activation of the mechanistic target of rapamycin complex 1 (mTORC1), endoplasmic reticulum (ER) stress, and CD8+ T cell death. Protective CD8+ T cell responses in HSAN-I patient PBMCs and Sptlc2-deficient mice were restored by supplementing with sphingolipids and pharmacologically inhibiting ER stress-induced cell death. Therefore, SPTLC2 underpins protective immunity by translating extracellular stimuli into intracellular anabolic signals and antagonizes ER stress to promote T cell metabolic fitness.
DOI: 10.1016/j.immuni.2019.03.005
PubMed: 30952607
PubMed Central: PMC6531359
Affiliations:
- Allemagne, Autriche, Belgique, France, République tchèque, États-Unis
- Bade-Wurtemberg, Bavière, Bohême centrale, Californie, District de Haute-Bavière, District de Karlsruhe, Provence-Alpes-Côte d'Azur, Province d'Anvers, Région flamande, Vienne (Autriche)
- Anvers, Heidelberg, Marseille, Munich, Prague, Vienne (Autriche)
- Université d'Anvers
Links toward previous steps (curation, corpus...)
Le document en format XML
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German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Lipid Pathobiochemistry Group (G131), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Ming, Yanan" sort="Ming, Yanan" uniqKey="Ming Y" first="Yanan" last="Ming">Yanan Ming</name><affiliation wicri:level="3"><nlm:affiliation>Internal Medicine IV, University Heidelberg Hospital, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Internal Medicine IV, University Heidelberg Hospital, Im Neuenheimer Feld 345, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" 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Medical Genetics, Children Timone Hospital, 264 Rue Saint Pierre & Aix Marseille University, INSERM, MMG, U1251, 13385 Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Genetics, Children Timone Hospital, 264 Rue Saint Pierre & Aix Marseille University, INSERM, MMG, U1251, 13385 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Schlotter Weigel, Beate" sort="Schlotter Weigel, Beate" uniqKey="Schlotter Weigel B" first="Beate" last="Schlotter-Weigel">Beate Schlotter-Weigel</name><affiliation wicri:level="3"><nlm:affiliation>Friedrich-Baur-Institut, Neurologische Klinik and Poliklinik Ludwig-Maximilians-Universität, 80336 München, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Friedrich-Baur-Institut, Neurologische Klinik and 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P" first="Pavel" last="Seeman">Pavel Seeman</name><affiliation wicri:level="3"><nlm:affiliation>DNA Laboratory, Department of Child Neurology, 2nd Medical School, University Hospital Motol, Charles University, Prague, Czech Republic.</nlm:affiliation><country xml:lang="fr">République tchèque</country><wicri:regionArea>DNA Laboratory, Department of Child Neurology, 2nd Medical School, University Hospital Motol, Charles University, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Loscher, Wolfgang N" sort="Loscher, Wolfgang N" uniqKey="Loscher W" first="Wolfgang N" last="Löscher">Wolfgang N. Löscher</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Department of Neurology, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Clinical Department of Neurology, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck</wicri:regionArea><wicri:noRegion>6020 Innsbruck</wicri:noRegion></affiliation></author><author><name sortKey="Reindl, Markus" sort="Reindl, Markus" uniqKey="Reindl M" first="Markus" last="Reindl">Markus Reindl</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Department of Neurology, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Clinical Department of Neurology, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck</wicri:regionArea><wicri:noRegion>6020 Innsbruck</wicri:noRegion></affiliation></author><author><name sortKey="Weiss, Florian" 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92093</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Weisshaar, Nina" sort="Weisshaar, Nina" uniqKey="Weisshaar N" first="Nina" last="Weisshaar">Nina Weisshaar</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Madi, Alaa" sort="Madi, Alaa" uniqKey="Madi A" first="Alaa" last="Madi">Alaa Madi</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Mohr, Kerstin" sort="Mohr, Kerstin" uniqKey="Mohr K" first="Kerstin" last="Mohr">Kerstin Mohr</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Schlimbach, Tilo" sort="Schlimbach, Tilo" uniqKey="Schlimbach T" first="Tilo" last="Schlimbach">Tilo Schlimbach</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Velasco Cardenas, Rubi M H" sort="Velasco Cardenas, Rubi M H" uniqKey="Velasco Cardenas R" first="Rubí M-H" last="Velasco Cárdenas">Rubí M-H Velasco Cárdenas</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Koeppel, Jonas" sort="Koeppel, Jonas" uniqKey="Koeppel J" first="Jonas" last="Koeppel">Jonas Koeppel</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Grunschl Ger, Florian" sort="Grunschl Ger, Florian" uniqKey="Grunschl Ger F" first="Florian" last="Grünschl Ger">Florian Grünschl Ger</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Muller, Lisann" sort="Muller, Lisann" uniqKey="Muller L" first="Lisann" last="Müller">Lisann Müller</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Baumeister, Maren" sort="Baumeister, Maren" uniqKey="Baumeister M" first="Maren" last="Baumeister">Maren Baumeister</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Brugger, Britta" sort="Brugger, Britta" uniqKey="Brugger B" first="Britta" last="Brügger">Britta Brügger</name><affiliation wicri:level="3"><nlm:affiliation>Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Schmitt, Michael" sort="Schmitt, Michael" uniqKey="Schmitt M" first="Michael" last="Schmitt">Michael Schmitt</name><affiliation wicri:level="3"><nlm:affiliation>Internal Medicine V, University Heidelberg Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Internal Medicine V, University Heidelberg Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Wabnitz, Guido" sort="Wabnitz, Guido" uniqKey="Wabnitz G" first="Guido" last="Wabnitz">Guido Wabnitz</name><affiliation wicri:level="3"><nlm:affiliation>Section Molecular Immunology, Institute of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section Molecular Immunology, Institute of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Samstag, Yvonne" sort="Samstag, Yvonne" uniqKey="Samstag Y" first="Yvonne" last="Samstag">Yvonne Samstag</name><affiliation wicri:level="3"><nlm:affiliation>Section Molecular Immunology, Institute of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section Molecular Immunology, Institute of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Cui, Guoliang" sort="Cui, Guoliang" uniqKey="Cui G" first="Guoliang" last="Cui">Guoliang Cui</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany. Electronic address: g.cui@dkfz.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:30952607</idno><idno type="pmid">30952607</idno><idno type="doi">10.1016/j.immuni.2019.03.005</idno><idno type="pmc">PMC6531359</idno><idno type="wicri:Area/Main/Corpus">000306</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000306</idno><idno type="wicri:Area/Main/Curation">000306</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000306</idno><idno type="wicri:Area/Main/Exploration">000306</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8<sup>+</sup> T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness.</title><author><name sortKey="Wu, Jingxia" sort="Wu, Jingxia" uniqKey="Wu J" first="Jingxia" last="Wu">Jingxia Wu</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Ma, Sicong" sort="Ma, Sicong" uniqKey="Ma S" first="Sicong" last="Ma">Sicong Ma</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Medical Faculty Heidelberg, Heidelberg University, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Medical Faculty Heidelberg, Heidelberg University, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Sandhoff, Roger" sort="Sandhoff, Roger" uniqKey="Sandhoff R" first="Roger" last="Sandhoff">Roger Sandhoff</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Pathobiochemistry Group (G131), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Lipid Pathobiochemistry Group (G131), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Ming, Yanan" sort="Ming, Yanan" uniqKey="Ming Y" first="Yanan" last="Ming">Yanan Ming</name><affiliation wicri:level="3"><nlm:affiliation>Internal Medicine IV, University Heidelberg Hospital, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Internal Medicine IV, University Heidelberg Hospital, Im Neuenheimer Feld 345, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Hotz Wagenblatt, Agnes" sort="Hotz Wagenblatt, Agnes" uniqKey="Hotz Wagenblatt A" first="Agnes" last="Hotz-Wagenblatt">Agnes Hotz-Wagenblatt</name><affiliation wicri:level="3"><nlm:affiliation>Core Facility Omics IT and Data Management, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Core Facility Omics IT and Data Management, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Timmerman, Vincent" sort="Timmerman, Vincent" uniqKey="Timmerman V" first="Vincent" last="Timmerman">Vincent Timmerman</name><affiliation wicri:level="4"><nlm:affiliation>Peripheral Neuropathy Research Group, Department of Biomedical Sciences, Institute Born Bunge, B-2610, University of Antwerp, Antwerpen, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Peripheral Neuropathy Research Group, Department of Biomedical Sciences, Institute Born Bunge, B-2610, University of Antwerp, Antwerpen</wicri:regionArea><orgName type="university">Université d'Anvers</orgName><placeName><settlement type="city">Anvers</settlement><region>Région flamande</region><region type="district" nuts="2">Province d'Anvers</region></placeName></affiliation></author><author><name sortKey="Bonello Palot, Nathalie" sort="Bonello Palot, Nathalie" uniqKey="Bonello Palot N" first="Nathalie" last="Bonello-Palot">Nathalie Bonello-Palot</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Genetics, Children Timone Hospital, 264 Rue Saint Pierre & Aix Marseille University, INSERM, MMG, U1251, 13385 Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Genetics, Children Timone Hospital, 264 Rue Saint Pierre & Aix Marseille University, INSERM, MMG, U1251, 13385 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Schlotter Weigel, Beate" sort="Schlotter Weigel, Beate" uniqKey="Schlotter Weigel B" first="Beate" last="Schlotter-Weigel">Beate Schlotter-Weigel</name><affiliation wicri:level="3"><nlm:affiliation>Friedrich-Baur-Institut, Neurologische Klinik and Poliklinik Ludwig-Maximilians-Universität, 80336 München, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Friedrich-Baur-Institut, Neurologische Klinik and Poliklinik Ludwig-Maximilians-Universität, 80336 München</wicri:regionArea><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName></affiliation></author><author><name sortKey="Auer Grumbach, Michaela" sort="Auer Grumbach, Michaela" uniqKey="Auer Grumbach M" first="Michaela" last="Auer-Grumbach">Michaela Auer-Grumbach</name><affiliation wicri:level="3"><nlm:affiliation>Department of Orthopaedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Department of Orthopaedics and Trauma Surgery, Medical University of Vienna, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Seeman, Pavel" sort="Seeman, Pavel" uniqKey="Seeman P" first="Pavel" last="Seeman">Pavel Seeman</name><affiliation wicri:level="3"><nlm:affiliation>DNA Laboratory, Department of Child Neurology, 2nd Medical School, University Hospital Motol, Charles University, Prague, Czech Republic.</nlm:affiliation><country xml:lang="fr">République tchèque</country><wicri:regionArea>DNA Laboratory, Department of Child Neurology, 2nd Medical School, University Hospital Motol, Charles University, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Loscher, Wolfgang N" sort="Loscher, Wolfgang N" uniqKey="Loscher W" first="Wolfgang N" last="Löscher">Wolfgang N. Löscher</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Department of Neurology, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Clinical Department of Neurology, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck</wicri:regionArea><wicri:noRegion>6020 Innsbruck</wicri:noRegion></affiliation></author><author><name sortKey="Reindl, Markus" sort="Reindl, Markus" uniqKey="Reindl M" first="Markus" last="Reindl">Markus Reindl</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Department of Neurology, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Clinical Department of Neurology, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck</wicri:regionArea><wicri:noRegion>6020 Innsbruck</wicri:noRegion></affiliation></author><author><name sortKey="Weiss, Florian" sort="Weiss, Florian" uniqKey="Weiss F" first="Florian" last="Weiss">Florian Weiss</name><affiliation wicri:level="1"><nlm:affiliation>Department of Psychiatry and Psychotherapy, University Hospital of Psychiatry, Bolligenstrasse 111, 3000 Bern, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Psychiatry and Psychotherapy, University Hospital of Psychiatry, Bolligenstrasse 111, 3000 Bern</wicri:regionArea><wicri:noRegion>3000 Bern</wicri:noRegion><wicri:noRegion>3000 Bern</wicri:noRegion><wicri:noRegion>3000 Bern</wicri:noRegion></affiliation></author><author><name sortKey="Mah, Eric" sort="Mah, Eric" uniqKey="Mah E" first="Eric" last="Mah">Eric Mah</name><affiliation wicri:level="2"><nlm:affiliation>School of Medicine, UC San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>School of Medicine, UC San Diego, 9500 Gilman Drive, La Jolla, CA 92093</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Weisshaar, Nina" sort="Weisshaar, Nina" uniqKey="Weisshaar N" first="Nina" last="Weisshaar">Nina Weisshaar</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Madi, Alaa" sort="Madi, Alaa" uniqKey="Madi A" first="Alaa" last="Madi">Alaa Madi</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Mohr, Kerstin" sort="Mohr, Kerstin" uniqKey="Mohr K" first="Kerstin" last="Mohr">Kerstin Mohr</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Schlimbach, Tilo" sort="Schlimbach, Tilo" uniqKey="Schlimbach T" first="Tilo" last="Schlimbach">Tilo Schlimbach</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Velasco Cardenas, Rubi M H" sort="Velasco Cardenas, Rubi M H" uniqKey="Velasco Cardenas R" first="Rubí M-H" last="Velasco Cárdenas">Rubí M-H Velasco Cárdenas</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Koeppel, Jonas" sort="Koeppel, Jonas" uniqKey="Koeppel J" first="Jonas" last="Koeppel">Jonas Koeppel</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Grunschl Ger, Florian" sort="Grunschl Ger, Florian" uniqKey="Grunschl Ger F" first="Florian" last="Grünschl Ger">Florian Grünschl Ger</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Muller, Lisann" sort="Muller, Lisann" uniqKey="Muller L" first="Lisann" last="Müller">Lisann Müller</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Baumeister, Maren" sort="Baumeister, Maren" uniqKey="Baumeister M" first="Maren" last="Baumeister">Maren Baumeister</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Brugger, Britta" sort="Brugger, Britta" uniqKey="Brugger B" first="Britta" last="Brügger">Britta Brügger</name><affiliation wicri:level="3"><nlm:affiliation>Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Schmitt, Michael" sort="Schmitt, Michael" uniqKey="Schmitt M" first="Michael" last="Schmitt">Michael Schmitt</name><affiliation wicri:level="3"><nlm:affiliation>Internal Medicine V, University Heidelberg Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Internal Medicine V, University Heidelberg Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Wabnitz, Guido" sort="Wabnitz, Guido" uniqKey="Wabnitz G" first="Guido" last="Wabnitz">Guido Wabnitz</name><affiliation wicri:level="3"><nlm:affiliation>Section Molecular Immunology, Institute of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section Molecular Immunology, Institute of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Samstag, Yvonne" sort="Samstag, Yvonne" uniqKey="Samstag Y" first="Yvonne" last="Samstag">Yvonne Samstag</name><affiliation wicri:level="3"><nlm:affiliation>Section Molecular Immunology, Institute of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section Molecular Immunology, Institute of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Cui, Guoliang" sort="Cui, Guoliang" uniqKey="Cui G" first="Guoliang" last="Cui">Guoliang Cui</name><affiliation wicri:level="3"><nlm:affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany. Electronic address: g.cui@dkfz.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author></analytic><series><title level="j">Immunity</title><idno type="eISSN">1097-4180</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>CD8-Positive T-Lymphocytes (immunology)</term><term>Cell Proliferation (MeSH)</term><term>Cells, Cultured (MeSH)</term><term>Cytokines (biosynthesis)</term><term>Endoplasmic Reticulum Stress (genetics)</term><term>Endoplasmic Reticulum Stress (immunology)</term><term>Female (MeSH)</term><term>Hereditary Sensory and Autonomic Neuropathies (genetics)</term><term>Humans (MeSH)</term><term>Lymphocytic Choriomeningitis (immunology)</term><term>Lymphocytic Choriomeningitis (virology)</term><term>Lymphocytic choriomeningitis virus (immunology)</term><term>Male (MeSH)</term><term>Mechanistic Target of Rapamycin Complex 1 (metabolism)</term><term>Mice (MeSH)</term><term>Mice, Inbred C57BL (MeSH)</term><term>Middle Aged (MeSH)</term><term>Serine C-Palmitoyltransferase (genetics)</term><term>Signal Transduction (immunology)</term><term>Sphingolipids (biosynthesis)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen (MeSH)</term><term>Animaux (MeSH)</term><term>Cellules cultivées (MeSH)</term><term>Chorioméningite lymphocytaire (immunologie)</term><term>Chorioméningite lymphocytaire (virologie)</term><term>Complexe-1 cible mécanistique de la rapamycine (métabolisme)</term><term>Cytokines (biosynthèse)</term><term>Femelle (MeSH)</term><term>Humains (MeSH)</term><term>Lymphocytes T CD8+ (immunologie)</term><term>Mâle (MeSH)</term><term>Neuropathies héréditaires sensitives et autonomes (génétique)</term><term>Prolifération cellulaire (MeSH)</term><term>Serine C-palmitoyltransferase (génétique)</term><term>Souris (MeSH)</term><term>Souris de lignée C57BL (MeSH)</term><term>Sphingolipides (biosynthèse)</term><term>Stress du réticulum endoplasmique (génétique)</term><term>Stress du réticulum endoplasmique (immunologie)</term><term>Transduction du signal (immunologie)</term><term>Virus de la chorioméningite lymphocytaire (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Cytokines</term><term>Sphingolipids</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Cytokines</term><term>Sphingolipides</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Endoplasmic Reticulum Stress</term><term>Hereditary Sensory and Autonomic Neuropathies</term><term>Serine C-Palmitoyltransferase</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Neuropathies héréditaires sensitives et autonomes</term><term>Serine C-palmitoyltransferase</term><term>Stress du réticulum endoplasmique</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Chorioméningite lymphocytaire</term><term>Lymphocytes T CD8+</term><term>Stress du réticulum endoplasmique</term><term>Transduction du signal</term><term>Virus de la chorioméningite lymphocytaire</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term><term>Endoplasmic Reticulum Stress</term><term>Lymphocytic Choriomeningitis</term><term>Lymphocytic choriomeningitis virus</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Mechanistic Target of Rapamycin Complex 1</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Complexe-1 cible mécanistique de la rapamycine</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Chorioméningite lymphocytaire</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lymphocytic Choriomeningitis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Proliferation</term><term>Cells, Cultured</term><term>Female</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Middle Aged</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Animaux</term><term>Cellules cultivées</term><term>Femelle</term><term>Humains</term><term>Mâle</term><term>Prolifération cellulaire</term><term>Souris</term><term>Souris de lignée C57BL</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Patients with the neurological disorder HSAN-I suffer frequent infections, attributed to a lack of pain sensation and failure to seek care for minor injuries. Whether protective CD8<sup>+</sup> T cells are affected in HSAN-I patients remains unknown. Here, we report that HSAN-I-associated mutations in serine palmitoyltransferase subunit SPTLC2 dampened human T cell responses. Antigen stimulation and inflammation induced SPTLC2 expression, and murine T-cell-specific ablation of Sptlc2 impaired antiviral-T-cell expansion and effector function. Sptlc2 deficiency reduced sphingolipid biosynthetic flux and led to prolonged activation of the mechanistic target of rapamycin complex 1 (mTORC1), endoplasmic reticulum (ER) stress, and CD8<sup>+</sup> T cell death. Protective CD8<sup>+</sup> T cell responses in HSAN-I patient PBMCs and Sptlc2-deficient mice were restored by supplementing with sphingolipids and pharmacologically inhibiting ER stress-induced cell death. Therefore, SPTLC2 underpins protective immunity by translating extracellular stimuli into intracellular anabolic signals and antagonizes ER stress to promote T cell metabolic fitness.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30952607</PMID><DateCompleted><Year>2019</Year><Month>10</Month><Day>17</Day></DateCompleted><DateRevised><Year>2020</Year><Month>05</Month><Day>22</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1097-4180</ISSN><JournalIssue CitedMedium="Internet"><Volume>50</Volume><Issue>5</Issue><PubDate><Year>2019</Year><Month>05</Month><Day>21</Day></PubDate></JournalIssue><Title>Immunity</Title><ISOAbbreviation>Immunity</ISOAbbreviation></Journal><ArticleTitle>Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8<sup>+</sup> T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness.</ArticleTitle><Pagination><MedlinePgn>1218-1231.e5</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S1074-7613(19)30095-0</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.immuni.2019.03.005</ELocationID><Abstract><AbstractText>Patients with the neurological disorder HSAN-I suffer frequent infections, attributed to a lack of pain sensation and failure to seek care for minor injuries. Whether protective CD8<sup>+</sup> T cells are affected in HSAN-I patients remains unknown. Here, we report that HSAN-I-associated mutations in serine palmitoyltransferase subunit SPTLC2 dampened human T cell responses. Antigen stimulation and inflammation induced SPTLC2 expression, and murine T-cell-specific ablation of Sptlc2 impaired antiviral-T-cell expansion and effector function. Sptlc2 deficiency reduced sphingolipid biosynthetic flux and led to prolonged activation of the mechanistic target of rapamycin complex 1 (mTORC1), endoplasmic reticulum (ER) stress, and CD8<sup>+</sup> T cell death. Protective CD8<sup>+</sup> T cell responses in HSAN-I patient PBMCs and Sptlc2-deficient mice were restored by supplementing with sphingolipids and pharmacologically inhibiting ER stress-induced cell death. Therefore, SPTLC2 underpins protective immunity by translating extracellular stimuli into intracellular anabolic signals and antagonizes ER stress to promote T cell metabolic fitness.</AbstractText><CopyrightInformation>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Jingxia</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ma</LastName><ForeName>Sicong</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Medical Faculty Heidelberg, Heidelberg University, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sandhoff</LastName><ForeName>Roger</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Lipid Pathobiochemistry Group (G131), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ming</LastName><ForeName>Yanan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Internal Medicine IV, University Heidelberg Hospital, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hotz-Wagenblatt</LastName><ForeName>Agnes</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Core Facility Omics IT and Data Management, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Timmerman</LastName><ForeName>Vincent</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Peripheral Neuropathy Research Group, Department of Biomedical Sciences, Institute Born Bunge, B-2610, University of Antwerp, Antwerpen, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bonello-Palot</LastName><ForeName>Nathalie</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Medical Genetics, Children Timone Hospital, 264 Rue Saint Pierre & Aix Marseille University, INSERM, MMG, U1251, 13385 Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schlotter-Weigel</LastName><ForeName>Beate</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Friedrich-Baur-Institut, Neurologische Klinik and Poliklinik Ludwig-Maximilians-Universität, 80336 München, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Auer-Grumbach</LastName><ForeName>Michaela</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Orthopaedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Seeman</LastName><ForeName>Pavel</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>DNA Laboratory, Department of Child Neurology, 2nd Medical School, University Hospital Motol, Charles University, Prague, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Löscher</LastName><ForeName>Wolfgang N</ForeName><Initials>WN</Initials><AffiliationInfo><Affiliation>Clinical Department of Neurology, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Reindl</LastName><ForeName>Markus</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Clinical Department of Neurology, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Weiss</LastName><ForeName>Florian</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Psychiatry and Psychotherapy, University Hospital of Psychiatry, Bolligenstrasse 111, 3000 Bern, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mah</LastName><ForeName>Eric</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>School of Medicine, UC San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Weisshaar</LastName><ForeName>Nina</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Madi</LastName><ForeName>Alaa</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mohr</LastName><ForeName>Kerstin</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schlimbach</LastName><ForeName>Tilo</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Velasco Cárdenas</LastName><ForeName>Rubí M-H</ForeName><Initials>RM</Initials><AffiliationInfo><Affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Koeppel</LastName><ForeName>Jonas</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Grünschläger</LastName><ForeName>Florian</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Müller</LastName><ForeName>Lisann</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baumeister</LastName><ForeName>Maren</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brügger</LastName><ForeName>Britta</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schmitt</LastName><ForeName>Michael</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Internal Medicine V, University Heidelberg Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wabnitz</LastName><ForeName>Guido</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Section Molecular Immunology, Institute of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Samstag</LastName><ForeName>Yvonne</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Section Molecular Immunology, Institute of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cui</LastName><ForeName>Guoliang</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany. Electronic address: g.cui@dkfz.de.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>P 27634</GrantID><Acronym>FWF_</Acronym><Agency>Austrian Science Fund FWF</Agency><Country>Austria</Country></Grant><Grant><GrantID>UL1 TR001442</GrantID><Acronym>TR</Acronym><Agency>NCATS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>04</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Immunity</MedlineTA><NlmUniqueID>9432918</NlmUniqueID><ISSNLinking>1074-7613</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016207">Cytokines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013107">Sphingolipids</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.3.1.50</RegistryNumber><NameOfSubstance UI="C495089">SPTLC2 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.3.1.50</RegistryNumber><NameOfSubstance UI="D051102">Serine C-Palmitoyltransferase</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D000076222">Mechanistic Target of Rapamycin Complex 1</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018414" MajorTopicYN="N">CD8-Positive T-Lymphocytes</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016207" MajorTopicYN="N">Cytokines</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D059865" MajorTopicYN="N">Endoplasmic Reticulum Stress</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009477" MajorTopicYN="N">Hereditary Sensory and Autonomic Neuropathies</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008216" MajorTopicYN="N">Lymphocytic Choriomeningitis</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008217" MajorTopicYN="N">Lymphocytic choriomeningitis virus</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000076222" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 1</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051102" MajorTopicYN="N">Serine C-Palmitoyltransferase</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013107" MajorTopicYN="N">Sphingolipids</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">CD8+ T cells</Keyword><Keyword MajorTopicYN="Y">ER stress</Keyword><Keyword MajorTopicYN="Y">HSAN-I</Keyword><Keyword MajorTopicYN="Y">SPTLC2</Keyword><Keyword MajorTopicYN="Y">neurological diseases</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>04</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>01</Month><Day>07</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>03</Month><Day>06</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>4</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>10</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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tchèque</li><li>États-Unis</li></country><region><li>Bade-Wurtemberg</li><li>Bavière</li><li>Bohême centrale</li><li>Californie</li><li>District de Haute-Bavière</li><li>District de Karlsruhe</li><li>Provence-Alpes-Côte d'Azur</li><li>Province d'Anvers</li><li>Région flamande</li><li>Vienne (Autriche)</li></region><settlement><li>Anvers</li><li>Heidelberg</li><li>Marseille</li><li>Munich</li><li>Prague</li><li>Vienne (Autriche)</li></settlement><orgName><li>Université d'Anvers</li></orgName></list><tree><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Wu, Jingxia" sort="Wu, Jingxia" uniqKey="Wu J" first="Jingxia" last="Wu">Jingxia Wu</name></region><name sortKey="Baumeister, Maren" sort="Baumeister, Maren" uniqKey="Baumeister M" first="Maren" last="Baumeister">Maren Baumeister</name><name sortKey="Brugger, Britta" sort="Brugger, Britta" uniqKey="Brugger B" first="Britta" last="Brügger">Britta Brügger</name><name sortKey="Cui, Guoliang" sort="Cui, Guoliang" uniqKey="Cui G" first="Guoliang" last="Cui">Guoliang Cui</name><name sortKey="Grunschl Ger, Florian" sort="Grunschl Ger, Florian" uniqKey="Grunschl Ger F" first="Florian" last="Grünschl Ger">Florian Grünschl Ger</name><name sortKey="Hotz Wagenblatt, Agnes" sort="Hotz Wagenblatt, Agnes" uniqKey="Hotz Wagenblatt A" first="Agnes" last="Hotz-Wagenblatt">Agnes Hotz-Wagenblatt</name><name sortKey="Koeppel, Jonas" sort="Koeppel, Jonas" uniqKey="Koeppel J" first="Jonas" last="Koeppel">Jonas Koeppel</name><name sortKey="Ma, Sicong" sort="Ma, Sicong" uniqKey="Ma S" first="Sicong" last="Ma">Sicong Ma</name><name sortKey="Madi, Alaa" sort="Madi, Alaa" uniqKey="Madi A" first="Alaa" last="Madi">Alaa Madi</name><name sortKey="Ming, Yanan" sort="Ming, Yanan" uniqKey="Ming Y" first="Yanan" last="Ming">Yanan Ming</name><name sortKey="Mohr, Kerstin" sort="Mohr, Kerstin" uniqKey="Mohr K" first="Kerstin" last="Mohr">Kerstin Mohr</name><name sortKey="Muller, Lisann" sort="Muller, Lisann" uniqKey="Muller L" first="Lisann" last="Müller">Lisann Müller</name><name sortKey="Samstag, Yvonne" sort="Samstag, Yvonne" uniqKey="Samstag Y" first="Yvonne" last="Samstag">Yvonne Samstag</name><name sortKey="Sandhoff, Roger" sort="Sandhoff, Roger" uniqKey="Sandhoff R" first="Roger" last="Sandhoff">Roger Sandhoff</name><name sortKey="Schlimbach, Tilo" sort="Schlimbach, Tilo" uniqKey="Schlimbach T" first="Tilo" last="Schlimbach">Tilo Schlimbach</name><name sortKey="Schlotter Weigel, Beate" sort="Schlotter Weigel, Beate" uniqKey="Schlotter Weigel B" first="Beate" last="Schlotter-Weigel">Beate Schlotter-Weigel</name><name sortKey="Schmitt, Michael" sort="Schmitt, Michael" uniqKey="Schmitt M" first="Michael" last="Schmitt">Michael Schmitt</name><name sortKey="Velasco Cardenas, Rubi M H" sort="Velasco Cardenas, Rubi M H" uniqKey="Velasco Cardenas R" first="Rubí M-H" last="Velasco Cárdenas">Rubí M-H Velasco Cárdenas</name><name sortKey="Wabnitz, Guido" sort="Wabnitz, Guido" uniqKey="Wabnitz G" first="Guido" last="Wabnitz">Guido Wabnitz</name><name sortKey="Weiss, Florian" sort="Weiss, Florian" uniqKey="Weiss F" first="Florian" last="Weiss">Florian Weiss</name><name sortKey="Weisshaar, Nina" sort="Weisshaar, Nina" uniqKey="Weisshaar N" first="Nina" last="Weisshaar">Nina Weisshaar</name></country><country name="Belgique"><region name="Région flamande"><name sortKey="Timmerman, Vincent" sort="Timmerman, Vincent" uniqKey="Timmerman V" first="Vincent" last="Timmerman">Vincent Timmerman</name></region></country><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Bonello Palot, Nathalie" sort="Bonello Palot, Nathalie" uniqKey="Bonello Palot N" first="Nathalie" last="Bonello-Palot">Nathalie Bonello-Palot</name></region></country><country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Auer Grumbach, Michaela" sort="Auer Grumbach, Michaela" uniqKey="Auer Grumbach M" first="Michaela" last="Auer-Grumbach">Michaela Auer-Grumbach</name></region><name sortKey="Loscher, Wolfgang N" sort="Loscher, Wolfgang N" uniqKey="Loscher W" first="Wolfgang N" last="Löscher">Wolfgang N. Löscher</name><name sortKey="Reindl, Markus" sort="Reindl, Markus" uniqKey="Reindl M" first="Markus" last="Reindl">Markus Reindl</name></country><country name="République tchèque"><region name="Bohême centrale"><name sortKey="Seeman, Pavel" sort="Seeman, Pavel" uniqKey="Seeman P" first="Pavel" last="Seeman">Pavel Seeman</name></region></country><country name="États-Unis"><region name="Californie"><name sortKey="Mah, Eric" sort="Mah, Eric" uniqKey="Mah E" first="Eric" last="Mah">Eric Mah</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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