Glucocorticoid-Induced Leucine Zipper Protein Controls Macropinocytosis in Dendritic Cells.
Identifieur interne : 003D85 ( Ncbi/Curation ); précédent : 003D84; suivant : 003D86Glucocorticoid-Induced Leucine Zipper Protein Controls Macropinocytosis in Dendritic Cells.
Auteurs : Joseph Calmette [France] ; Matthieu Bertrand [France] ; Mathias Vétillard [France] ; Mehdi Ellouze [France] ; Shaun Flint [Royaume-Uni] ; Valérie Nicolas [France] ; Armelle Biola-Vidamment [France] ; Marc Pallardy [France] ; Eric Morand [Australie] ; Françoise Bachelerie [France] ; Véronique Godot [France] ; Géraldine Schlecht-Louf [France]Source :
- Journal of immunology (Baltimore, Md. : 1950) [ 1550-6606 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Antigènes (génétique), Antigènes (immunologie), Cellules dendritiques (immunologie), Facteurs de transcription (génétique), Facteurs de transcription (immunologie), Lymphocytes T CD8+ (immunologie), Lymphocytes T régulateurs (immunologie), Pinocytose (génétique), Pinocytose (immunologie), Présentation d'antigène, Souris, Souris transgéniques.
- MESH :
English descriptors
- KwdEn :
- Animals, Antigen Presentation, Antigens (genetics), Antigens (immunology), CD8-Positive T-Lymphocytes (immunology), Dendritic Cells (immunology), Mice, Mice, Transgenic, Pinocytosis (genetics), Pinocytosis (immunology), T-Lymphocytes, Regulatory (immunology), Transcription Factors (genetics), Transcription Factors (immunology).
- MESH :
- chemical , genetics : Antigens, Transcription Factors.
- chemical , immunology : Antigens, Transcription Factors.
- genetics : Pinocytosis.
- immunology : CD8-Positive T-Lymphocytes, Dendritic Cells, Pinocytosis, T-Lymphocytes, Regulatory.
- Animals, Antigen Presentation, Mice, Mice, Transgenic.
Abstract
Ag sampling is a key process in dendritic cell (DC) biology. DCs use constitutive macropinocytosis, receptor-mediated endocytosis, and phagocytosis to capture exogenous Ags for presentation to T cells. We investigated the mechanisms that regulate Ag uptake by DCs in the steady-state and after a short-term LPS exposure in vitro and in vivo. We show that the glucocorticoid-induced leucine zipper protein (GILZ), already known to regulate effector versus regulatory T cell activation by DCs, selectively limits macropinocytosis, but not receptor-mediated phagocytosis, in immature and recently activated DCs. In vivo, the GILZ-mediated inhibition of Ag uptake is restricted to the CD8α(+) DC subset, which expresses the highest GILZ level among splenic DC subsets. In recently activated DCs, we further establish that GILZ limits p38 MAPK phosphorylation, providing a possible mechanism for GILZ-mediated macropinocytosis control. Finally, our results demonstrate that the modulation of Ag uptake by GILZ does not result in altered Ag presentation to CD4 T cells but impacts the efficiency of cross-presentation to CD8 T cells. Altogether, our results identify GILZ as an endogenous inhibitor of macropinocytosis in DCs, the action of which contributes to the fine-tuning of Ag cross-presentation.
DOI: 10.4049/jimmunol.1600561
PubMed: 27793999
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Université Paris-Saclay, Chatenay Malabry 92296, France; and.</nlm:affiliation><orgName type="university">Université Paris-Sud</orgName><country>France</country><placeName><settlement type="city">Orsay</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Morand, Eric" sort="Morand, Eric" uniqKey="Morand E" first="Eric" last="Morand">Eric Morand</name><affiliation wicri:level="1"><nlm:affiliation>Southern Clinical School, Monash University Faculty of Medicine, Nursing, and Health Sciences, Clayton, Victoria 3168, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Southern Clinical School, Monash University Faculty of Medicine, Nursing, and Health Sciences, Clayton, Victoria 3168</wicri:regionArea><wicri:noRegion>Victoria 3168</wicri:noRegion></affiliation></author><author><name sortKey="Bachelerie, Francoise" sort="Bachelerie, Francoise" uniqKey="Bachelerie F" first="Françoise" 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xml:lang="fr">France</country><wicri:regionArea>UMR955, Team 16, Institut de Recherche Vaccinal, INSERM, Université Paris Est Créteil, Créteil 94010</wicri:regionArea><wicri:noRegion>94010</wicri:noRegion><wicri:noRegion>94010</wicri:noRegion></affiliation></author><author><name sortKey="Schlecht Louf, Geraldine" sort="Schlecht Louf, Geraldine" uniqKey="Schlecht Louf G" first="Géraldine" last="Schlecht-Louf">Géraldine Schlecht-Louf</name><affiliation wicri:level="4"><nlm:affiliation>UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140, France; geraldine.schlecht-louf@u-psud.fr.</nlm:affiliation><country wicri:rule="url">France</country><wicri:regionArea>UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140</wicri:regionArea><wicri:noRegion>92140</wicri:noRegion><orgName type="university">Université Paris-Sud</orgName><placeName><settlement 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Controls Macropinocytosis in Dendritic Cells.</title><author><name sortKey="Calmette, Joseph" sort="Calmette, Joseph" uniqKey="Calmette J" first="Joseph" last="Calmette">Joseph Calmette</name><affiliation wicri:level="4"><nlm:affiliation>UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Orsay</settlement></placeName><orgName type="university">Université Paris-Sud</orgName></affiliation></author><author><name sortKey="Bertrand, Matthieu" sort="Bertrand, Matthieu" uniqKey="Bertrand M" first="Matthieu" last="Bertrand">Matthieu Bertrand</name><affiliation wicri:level="4"><nlm:affiliation>UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140</wicri:regionArea><wicri:noRegion>92140</wicri:noRegion><orgName type="university">Université Paris-Sud</orgName><placeName><settlement type="city">Orsay</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Vetillard, Mathias" sort="Vetillard, Mathias" uniqKey="Vetillard M" first="Mathias" last="Vétillard">Mathias Vétillard</name><affiliation wicri:level="4"><nlm:affiliation>UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140</wicri:regionArea><wicri:noRegion>92140</wicri:noRegion><orgName type="university">Université Paris-Sud</orgName><placeName><settlement type="city">Orsay</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Ellouze, Mehdi" sort="Ellouze, Mehdi" uniqKey="Ellouze M" first="Mehdi" last="Ellouze">Mehdi Ellouze</name><affiliation wicri:level="1"><nlm:affiliation>UMR955, Team 16, Institut de Recherche Vaccinal, INSERM, Université Paris Est Créteil, Créteil 94010, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>UMR955, Team 16, Institut de Recherche Vaccinal, INSERM, Université Paris Est Créteil, Créteil 94010</wicri:regionArea><wicri:noRegion>94010</wicri:noRegion><wicri:noRegion>94010</wicri:noRegion></affiliation></author><author><name sortKey="Flint, Shaun" sort="Flint, Shaun" uniqKey="Flint S" first="Shaun" last="Flint">Shaun Flint</name><affiliation wicri:level="1"><nlm:affiliation>Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Addenbrooke's Hospital, Cambridge CB2 0QQ</wicri:regionArea><wicri:noRegion>Cambridge CB2 0QQ</wicri:noRegion></affiliation></author><author><name sortKey="Nicolas, Valerie" sort="Nicolas, Valerie" uniqKey="Nicolas V" first="Valérie" last="Nicolas">Valérie Nicolas</name><affiliation wicri:level="1"><nlm:affiliation>Institut Paris-Sud d'Innovation Thérapeutique, SFR-UMS, Chatenay Malabry 92296, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Paris-Sud d'Innovation Thérapeutique, SFR-UMS, Chatenay Malabry 92296</wicri:regionArea><wicri:noRegion>92296</wicri:noRegion><wicri:noRegion>92296</wicri:noRegion></affiliation></author><author><name sortKey="Biola Vidamment, Armelle" sort="Biola Vidamment, Armelle" uniqKey="Biola Vidamment A" first="Armelle" last="Biola-Vidamment">Armelle Biola-Vidamment</name><affiliation wicri:level="4"><nlm:affiliation>UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Chatenay Malabry 92296, France; and.</nlm:affiliation><orgName type="university">Université Paris-Sud</orgName><country>France</country><placeName><settlement type="city">Orsay</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Pallardy, Marc" sort="Pallardy, Marc" uniqKey="Pallardy M" first="Marc" last="Pallardy">Marc Pallardy</name><affiliation wicri:level="4"><nlm:affiliation>UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Chatenay Malabry 92296, France; and.</nlm:affiliation><orgName type="university">Université Paris-Sud</orgName><country>France</country><placeName><settlement type="city">Orsay</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Morand, Eric" sort="Morand, Eric" uniqKey="Morand E" first="Eric" last="Morand">Eric Morand</name><affiliation wicri:level="1"><nlm:affiliation>Southern Clinical School, Monash University Faculty of Medicine, Nursing, and Health Sciences, Clayton, Victoria 3168, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Southern Clinical School, Monash University Faculty of Medicine, Nursing, and Health Sciences, Clayton, Victoria 3168</wicri:regionArea><wicri:noRegion>Victoria 3168</wicri:noRegion></affiliation></author><author><name sortKey="Bachelerie, Francoise" sort="Bachelerie, Francoise" uniqKey="Bachelerie F" first="Françoise" last="Bachelerie">Françoise Bachelerie</name><affiliation wicri:level="4"><nlm:affiliation>UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140</wicri:regionArea><wicri:noRegion>92140</wicri:noRegion><orgName type="university">Université Paris-Sud</orgName><placeName><settlement type="city">Orsay</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Godot, Veronique" sort="Godot, Veronique" uniqKey="Godot V" first="Véronique" last="Godot">Véronique Godot</name><affiliation wicri:level="1"><nlm:affiliation>UMR955, Team 16, Institut de Recherche Vaccinal, INSERM, Université Paris Est Créteil, Créteil 94010, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>UMR955, Team 16, Institut de Recherche Vaccinal, INSERM, Université Paris Est Créteil, Créteil 94010</wicri:regionArea><wicri:noRegion>94010</wicri:noRegion><wicri:noRegion>94010</wicri:noRegion></affiliation></author><author><name sortKey="Schlecht Louf, Geraldine" sort="Schlecht Louf, Geraldine" uniqKey="Schlecht Louf G" first="Géraldine" last="Schlecht-Louf">Géraldine Schlecht-Louf</name><affiliation wicri:level="4"><nlm:affiliation>UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140, France; geraldine.schlecht-louf@u-psud.fr.</nlm:affiliation><country wicri:rule="url">France</country><wicri:regionArea>UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140</wicri:regionArea><wicri:noRegion>92140</wicri:noRegion><orgName type="university">Université Paris-Sud</orgName><placeName><settlement type="city">Orsay</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author></analytic><series><title level="j">Journal of immunology (Baltimore, Md. : 1950)</title><idno type="eISSN">1550-6606</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antigen Presentation</term><term>Antigens (genetics)</term><term>Antigens (immunology)</term><term>CD8-Positive T-Lymphocytes (immunology)</term><term>Dendritic Cells (immunology)</term><term>Mice</term><term>Mice, Transgenic</term><term>Pinocytosis (genetics)</term><term>Pinocytosis (immunology)</term><term>T-Lymphocytes, Regulatory (immunology)</term><term>Transcription Factors (genetics)</term><term>Transcription Factors (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antigènes (génétique)</term><term>Antigènes (immunologie)</term><term>Cellules dendritiques (immunologie)</term><term>Facteurs de transcription (génétique)</term><term>Facteurs de transcription (immunologie)</term><term>Lymphocytes T CD8+ (immunologie)</term><term>Lymphocytes T régulateurs (immunologie)</term><term>Pinocytose (génétique)</term><term>Pinocytose (immunologie)</term><term>Présentation d'antigène</term><term>Souris</term><term>Souris transgéniques</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antigens</term><term>Transcription Factors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens</term><term>Transcription Factors</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Pinocytosis</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes</term><term>Facteurs de transcription</term><term>Pinocytose</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes</term><term>Cellules dendritiques</term><term>Facteurs de transcription</term><term>Lymphocytes T CD8+</term><term>Lymphocytes T régulateurs</term><term>Pinocytose</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term><term>Dendritic Cells</term><term>Pinocytosis</term><term>T-Lymphocytes, Regulatory</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Antigen Presentation</term><term>Mice</term><term>Mice, Transgenic</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Présentation d'antigène</term><term>Souris</term><term>Souris transgéniques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Ag sampling is a key process in dendritic cell (DC) biology. DCs use constitutive macropinocytosis, receptor-mediated endocytosis, and phagocytosis to capture exogenous Ags for presentation to T cells. We investigated the mechanisms that regulate Ag uptake by DCs in the steady-state and after a short-term LPS exposure in vitro and in vivo. We show that the glucocorticoid-induced leucine zipper protein (GILZ), already known to regulate effector versus regulatory T cell activation by DCs, selectively limits macropinocytosis, but not receptor-mediated phagocytosis, in immature and recently activated DCs. In vivo, the GILZ-mediated inhibition of Ag uptake is restricted to the CD8α(+) DC subset, which expresses the highest GILZ level among splenic DC subsets. In recently activated DCs, we further establish that GILZ limits p38 MAPK phosphorylation, providing a possible mechanism for GILZ-mediated macropinocytosis control. Finally, our results demonstrate that the modulation of Ag uptake by GILZ does not result in altered Ag presentation to CD4 T cells but impacts the efficiency of cross-presentation to CD8 T cells. Altogether, our results identify GILZ as an endogenous inhibitor of macropinocytosis in DCs, the action of which contributes to the fine-tuning of Ag cross-presentation.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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