Serveur d'exploration sur les relations entre la France et l'Australie

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STAT3 is a critical cell-intrinsic regulator of human unconventional T cell numbers and function

Identifieur interne : 002532 ( Ncbi/Merge ); précédent : 002531; suivant : 002533

STAT3 is a critical cell-intrinsic regulator of human unconventional T cell numbers and function

Auteurs : Robert P. Wilson ; Megan L. Ives ; Geetha Rao ; Anthony Lau ; Kathryn Payne ; Masao Kobayashi ; Peter D. Arkwright ; Jane Peake ; Melanie Wong ; Stephen Adelstein ; Joanne M. Smart ; Martyn A. French ; David A. Fulcher ; Capucine Picard ; Jacinta Bustamante ; Stephanie Boisson-Dupuis ; Paul Gray ; Polina Stepensky ; Klaus Warnatz ; Alexandra F. Freeman ; Jamie Rossjohn ; James Mccluskey ; Steven M. Holland ; Jean-Laurent Casanova ; Gulbu Uzel ; Cindy S. Ma ; Stuart G. Tangye ; Elissa K. Deenick

Source :

RBID : PMC:4451129

Descripteurs français

English descriptors

Abstract

Wilson et al. show that individuals with loss-of-function mutations in STAT3 have reduced numbers of peripheral blood MAIT and NKT cells, but not γδ T cells. Residual MAIT cells had normal expression of RORγt, but displayed impaired secretion of IL-17A and IL-17F.


Url:
DOI: 10.1084/jem.20141992
PubMed: 25941256
PubMed Central: 4451129

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PMC:4451129

Le document en format XML

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<nlm:aff wicri:cut=" and" id="aff13">
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<affiliation>
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</affiliation>
</author>
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<institution>School of Women’s and Children’s Health, University of New South Wales, Sydney, NSW 2052, Australia</institution>
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<nlm:aff id="aff17">
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</nlm:aff>
</affiliation>
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<institution>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065</institution>
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<affiliation>
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<institution>St. Vincent’s Clinical School</institution>
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<institution>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia</institution>
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<affiliation>
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<institution>St. Vincent’s Clinical School</institution>
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</analytic>
<series>
<title level="j">The Journal of Experimental Medicine</title>
<idno type="ISSN">0022-1007</idno>
<idno type="eISSN">1540-9538</idno>
<imprint>
<date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Cell Separation</term>
<term>Cytokines (metabolism)</term>
<term>Flow Cytometry</term>
<term>Humans</term>
<term>Interferon-gamma (metabolism)</term>
<term>Interleukin-17 (metabolism)</term>
<term>Interleukin-23 (metabolism)</term>
<term>Interleukins (metabolism)</term>
<term>Killer Cells, Natural (cytology)</term>
<term>Leukocytes, Mononuclear (cytology)</term>
<term>Lymphocytes (cytology)</term>
<term>Mutation</term>
<term>Nuclear Receptor Subfamily 1, Group F, Member 3 (metabolism)</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Receptors, Antigen, T-Cell, gamma-delta (metabolism)</term>
<term>Receptors, Interleukin (metabolism)</term>
<term>Receptors, Interleukin-12 (metabolism)</term>
<term>Receptors, Interleukin-21 (metabolism)</term>
<term>STAT3 Transcription Factor (metabolism)</term>
<term>Signal Transduction</term>
<term>T-Lymphocytes (cytology)</term>
<term>Tumor Necrosis Factor-alpha (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Agranulocytes (cytologie)</term>
<term>Cellules tueuses naturelles (cytologie)</term>
<term>Cytokines (métabolisme)</term>
<term>Cytométrie en flux</term>
<term>Facteur de nécrose tumorale alpha (métabolisme)</term>
<term>Facteur de transcription STAT-3 (métabolisme)</term>
<term>Humains</term>
<term>Interféron gamma (métabolisme)</term>
<term>Interleukine-17 (métabolisme)</term>
<term>Interleukine-23 (métabolisme)</term>
<term>Interleukines (métabolisme)</term>
<term>Lymphocytes (cytologie)</term>
<term>Lymphocytes T (cytologie)</term>
<term>Membre-3 du groupe F de la sous-famille-1 de récepteurs nucléaires (métabolisme)</term>
<term>Mutation</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Récepteur lymphocytaire T antigène, gamma-delta (métabolisme)</term>
<term>Récepteurs aux interleukines (métabolisme)</term>
<term>Récepteurs à l'interleukine-12 (métabolisme)</term>
<term>Récepteurs à l'interleukine-21 (métabolisme)</term>
<term>Séparation cellulaire</term>
<term>Transduction du signal</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Cytokines</term>
<term>Interferon-gamma</term>
<term>Interleukin-17</term>
<term>Interleukin-23</term>
<term>Interleukins</term>
<term>Nuclear Receptor Subfamily 1, Group F, Member 3</term>
<term>Receptors, Antigen, T-Cell, gamma-delta</term>
<term>Receptors, Interleukin</term>
<term>Receptors, Interleukin-12</term>
<term>Receptors, Interleukin-21</term>
<term>STAT3 Transcription Factor</term>
<term>Tumor Necrosis Factor-alpha</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr">
<term>Agranulocytes</term>
<term>Cellules tueuses naturelles</term>
<term>Lymphocytes</term>
<term>Lymphocytes T</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en">
<term>Killer Cells, Natural</term>
<term>Leukocytes, Mononuclear</term>
<term>Lymphocytes</term>
<term>T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Cytokines</term>
<term>Facteur de nécrose tumorale alpha</term>
<term>Facteur de transcription STAT-3</term>
<term>Interféron gamma</term>
<term>Interleukine-17</term>
<term>Interleukine-23</term>
<term>Interleukines</term>
<term>Membre-3 du groupe F de la sous-famille-1 de récepteurs nucléaires</term>
<term>Récepteur lymphocytaire T antigène, gamma-delta</term>
<term>Récepteurs aux interleukines</term>
<term>Récepteurs à l'interleukine-12</term>
<term>Récepteurs à l'interleukine-21</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Cell Separation</term>
<term>Flow Cytometry</term>
<term>Humans</term>
<term>Mutation</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Cytométrie en flux</term>
<term>Humains</term>
<term>Mutation</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Séparation cellulaire</term>
<term>Transduction du signal</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Wilson et al. show that individuals with loss-of-function mutations in
<italic>STAT3</italic>
have reduced numbers of peripheral blood MAIT and NKT cells, but not γδ T cells. Residual MAIT cells had normal expression of RORγt, but displayed impaired secretion of IL-17A and IL-17F.</p>
</div>
</front>
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<affiliation>
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<institution>St. Vincent’s Clinical School</institution>
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<author>
<name sortKey="Lau, Anthony" sort="Lau, Anthony" uniqKey="Lau A" first="Anthony" last="Lau">Anthony Lau</name>
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<institution>University of Bath, Bath BA2 7AY, England, UK</institution>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">
<institution>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia</institution>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Payne, Kathryn" sort="Payne, Kathryn" uniqKey="Payne K" first="Kathryn" last="Payne">Kathryn Payne</name>
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<nlm:aff id="aff2">
<institution>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia</institution>
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<name sortKey="Kobayashi, Masao" sort="Kobayashi, Masao" uniqKey="Kobayashi M" first="Masao" last="Kobayashi">Masao Kobayashi</name>
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<nlm:aff id="aff4">
<institution>Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan 739-8511</institution>
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<affiliation>
<nlm:aff id="aff5">
<institution>University of Manchester, Royal Manchester Children’s Hospital, Manchester M13 9WL, England, UK</institution>
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</affiliation>
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<author>
<name sortKey="Peake, Jane" sort="Peake, Jane" uniqKey="Peake J" first="Jane" last="Peake">Jane Peake</name>
<affiliation>
<nlm:aff id="aff6">
<institution>Department of Paediatrics and Child Health, Royal Children’s Hospital Brisbane, Brisbane, QLD 4006, Australia</institution>
</nlm:aff>
</affiliation>
</author>
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<name sortKey="Wong, Melanie" sort="Wong, Melanie" uniqKey="Wong M" first="Melanie" last="Wong">Melanie Wong</name>
<affiliation>
<nlm:aff id="aff7">
<institution>Department of Allergy and Immunology, Children’s Hospital at Westmead, Westmead, Sydney, NSW 2145, Australia</institution>
</nlm:aff>
</affiliation>
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<name sortKey="Adelstein, Stephen" sort="Adelstein, Stephen" uniqKey="Adelstein S" first="Stephen" last="Adelstein">Stephen Adelstein</name>
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<nlm:aff id="aff8">
<institution>Department of Clinical Immunology, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW 2050, Australia</institution>
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<name sortKey="Smart, Joanne M" sort="Smart, Joanne M" uniqKey="Smart J" first="Joanne M." last="Smart">Joanne M. Smart</name>
<affiliation>
<nlm:aff id="aff9">
<institution>Department of Allergy and Immunology, Royal Children’s Hospital Melbourne, Parkville, VIC 3052, Australia</institution>
</nlm:aff>
</affiliation>
</author>
<author>
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<affiliation>
<nlm:aff id="aff10">
<institution>Department of Clinical Immunology, Royal Perth Hospital, Perth, WA 6000, Australia</institution>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff11">
<institution>School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, WA 6009, Australia</institution>
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<affiliation>
<nlm:aff id="aff12">
<institution>Department of Immunology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, Sydney, NSW 2006, Australia</institution>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Picard, Capucine" sort="Picard, Capucine" uniqKey="Picard C" first="Capucine" last="Picard">Capucine Picard</name>
<affiliation>
<nlm:aff wicri:cut=" and" id="aff13">
<institution>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163</institution>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff14">
<institution>Study Center for Primary Immunodeficiencies, Assistance Publique–Hôpitaux de Paris (AP-HP), Necker Hospital, 75015 Paris, France</institution>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff15">
<institution>Imagine Institute, Paris Descartes University, 75015 Paris, France</institution>
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<name sortKey="Bustamante, Jacinta" sort="Bustamante, Jacinta" uniqKey="Bustamante J" first="Jacinta" last="Bustamante">Jacinta Bustamante</name>
<affiliation>
<nlm:aff wicri:cut=" and" id="aff13">
<institution>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163</institution>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff14">
<institution>Study Center for Primary Immunodeficiencies, Assistance Publique–Hôpitaux de Paris (AP-HP), Necker Hospital, 75015 Paris, France</institution>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff15">
<institution>Imagine Institute, Paris Descartes University, 75015 Paris, France</institution>
</nlm:aff>
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<nlm:aff wicri:cut=" and" id="aff13">
<institution>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163</institution>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff16">
<institution>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065</institution>
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<nlm:aff id="aff3">
<institution>School of Women’s and Children’s Health, University of New South Wales, Sydney, NSW 2052, Australia</institution>
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<nlm:aff id="aff17">
<institution>Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Hadassah Medical Center, Hebrew University Medical Center, Jerusalem 91120, Israel</institution>
</nlm:aff>
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<nlm:aff wicri:cut=" and" id="aff20">
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<affiliation>
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<nlm:aff id="aff22">
<institution>Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia</institution>
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<institution>Imagine Institute, Paris Descartes University, 75015 Paris, France</institution>
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<affiliation>
<nlm:aff id="aff16">
<institution>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065</institution>
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<affiliation>
<nlm:aff id="aff23">
<institution>Howard Hughes Medical Institute, New York, NY 10065</institution>
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<affiliation>
<nlm:aff wicri:cut=" and" id="aff3">
<institution>St. Vincent’s Clinical School</institution>
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<institution>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia</institution>
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<affiliation>
<nlm:aff wicri:cut=" and" id="aff3">
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</analytic>
<series>
<title level="j">The Journal of Experimental Medicine</title>
<idno type="ISSN">0022-1007</idno>
<idno type="eISSN">1540-9538</idno>
<imprint>
<date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Wilson et al. show that individuals with loss-of-function mutations in
<italic>STAT3</italic>
have reduced numbers of peripheral blood MAIT and NKT cells, but not γδ T cells. Residual MAIT cells had normal expression of RORγt, but displayed impaired secretion of IL-17A and IL-17F.</p>
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<nlm:affiliation>University of Bath, Bath BA2 7AY, England, UK Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.</nlm:affiliation>
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<name sortKey="Ives, Megan L" sort="Ives, Megan L" uniqKey="Ives M" first="Megan L" last="Ives">Megan L. Ives</name>
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<nlm:affiliation>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia St. Vincent's Clinical School and School of Women's and Children's Health, University of New South Wales, Sydney, NSW 2052, Australia.</nlm:affiliation>
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<nlm:affiliation>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.</nlm:affiliation>
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<nlm:affiliation>University of Bath, Bath BA2 7AY, England, UK Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.</nlm:affiliation>
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<nlm:affiliation>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.</nlm:affiliation>
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<nlm:affiliation>Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan 739-8511.</nlm:affiliation>
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<nlm:affiliation>Department of Allergy and Immunology, Children's Hospital at Westmead, Westmead, Sydney, NSW 2145, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Allergy and Immunology, Children's Hospital at Westmead, Westmead, Sydney, NSW 2145</wicri:regionArea>
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<nlm:affiliation>Department of Clinical Immunology, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW 2050, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Clinical Immunology, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW 2050</wicri:regionArea>
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<name sortKey="Smart, Joanne M" sort="Smart, Joanne M" uniqKey="Smart J" first="Joanne M" last="Smart">Joanne M. Smart</name>
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<country xml:lang="fr">Australie</country>
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<country xml:lang="fr">Australie</country>
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<name sortKey="Fulcher, David A" sort="Fulcher, David A" uniqKey="Fulcher D" first="David A" last="Fulcher">David A. Fulcher</name>
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<nlm:affiliation>Department of Immunology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, Sydney, NSW 2006, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
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<name sortKey="Bustamante, Jacinta" sort="Bustamante, Jacinta" uniqKey="Bustamante J" first="Jacinta" last="Bustamante">Jacinta Bustamante</name>
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<nlm:affiliation>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163 and Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, 75015 Paris, France Study Center for Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker Hospital, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
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<name sortKey="Boisson Dupuis, Stephanie" sort="Boisson Dupuis, Stephanie" uniqKey="Boisson Dupuis S" first="Stephanie" last="Boisson-Dupuis">Stephanie Boisson-Dupuis</name>
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<nlm:affiliation>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163 and Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, 75015 Paris, France St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
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<region type="state">État de New York</region>
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<wicri:cityArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163 and Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, 75015 Paris, France St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York</wicri:cityArea>
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<name sortKey="Gray, Paul" sort="Gray, Paul" uniqKey="Gray P" first="Paul" last="Gray">Paul Gray</name>
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<nlm:affiliation>Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Hadassah Medical Center, Hebrew University Medical Center, Jerusalem 91120, Israel.</nlm:affiliation>
<country xml:lang="fr">Israël</country>
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<country xml:lang="fr">Allemagne</country>
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<region type="land" nuts="1">Bade-Wurtemberg</region>
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<name sortKey="Freeman, Alexandra F" sort="Freeman, Alexandra F" uniqKey="Freeman A" first="Alexandra F" last="Freeman">Alexandra F. Freeman</name>
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<nlm:affiliation>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
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<name sortKey="Rossjohn, Jamie" sort="Rossjohn, Jamie" uniqKey="Rossjohn J" first="Jamie" last="Rossjohn">Jamie Rossjohn</name>
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<nlm:affiliation>Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian Research Council (ARC) Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian Research Council (ARC) Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, Wales, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
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<name sortKey="Mccluskey, James" sort="Mccluskey, James" uniqKey="Mccluskey J" first="James" last="Mccluskey">James Mccluskey</name>
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<name sortKey="Holland, Steven M" sort="Holland, Steven M" uniqKey="Holland S" first="Steven M" last="Holland">Steven M. Holland</name>
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<name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
<affiliation wicri:level="2">
<nlm:affiliation>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163 and Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, 75015 Paris, France Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163 and Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065 Howard Hughes Medical Institute, New York, NY 10065.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163 and Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, 75015 Paris, France Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163 and Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065 Howard Hughes Medical Institute, New York</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Uzel, Gulbu" sort="Uzel, Gulbu" uniqKey="Uzel G" first="Gulbu" last="Uzel">Gulbu Uzel</name>
<affiliation wicri:level="2">
<nlm:affiliation>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Ma, Cindy S" sort="Ma, Cindy S" uniqKey="Ma C" first="Cindy S" last="Ma">Cindy S. Ma</name>
<affiliation wicri:level="1">
<nlm:affiliation>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia St. Vincent's Clinical School and School of Women's and Children's Health, University of New South Wales, Sydney, NSW 2052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia St. Vincent's Clinical School and School of Women's and Children's Health, University of New South Wales, Sydney, NSW 2052</wicri:regionArea>
<wicri:noRegion>NSW 2052</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Tangye, Stuart G" sort="Tangye, Stuart G" uniqKey="Tangye S" first="Stuart G" last="Tangye">Stuart G. Tangye</name>
<affiliation wicri:level="1">
<nlm:affiliation>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia St. Vincent's Clinical School and School of Women's and Children's Health, University of New South Wales, Sydney, NSW 2052, Australia e.deenick@garvan.org.au s.tangye@garvan.org.au.</nlm:affiliation>
<country wicri:rule="url">Australie</country>
<wicri:regionArea>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia St. Vincent's Clinical School and School of Women's and Children's Health, University of New South Wales, Sydney, NSW 2052</wicri:regionArea>
<wicri:noRegion>NSW 2052</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Deenick, Elissa K" sort="Deenick, Elissa K" uniqKey="Deenick E" first="Elissa K" last="Deenick">Elissa K. Deenick</name>
<affiliation wicri:level="1">
<nlm:affiliation>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia St. Vincent's Clinical School and School of Women's and Children's Health, University of New South Wales, Sydney, NSW 2052, Australia e.deenick@garvan.org.au s.tangye@garvan.org.au.</nlm:affiliation>
<country wicri:rule="url">Australie</country>
<wicri:regionArea>Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia St. Vincent's Clinical School and School of Women's and Children's Health, University of New South Wales, Sydney, NSW 2052</wicri:regionArea>
<wicri:noRegion>NSW 2052</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j">The Journal of experimental medicine</title>
<idno type="eISSN">1540-9538</idno>
<imprint>
<date when="2015" type="published">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Cell Separation</term>
<term>Cytokines (metabolism)</term>
<term>Flow Cytometry</term>
<term>Humans</term>
<term>Interferon-gamma (metabolism)</term>
<term>Interleukin-17 (metabolism)</term>
<term>Interleukin-23 (metabolism)</term>
<term>Interleukins (metabolism)</term>
<term>Killer Cells, Natural (cytology)</term>
<term>Leukocytes, Mononuclear (cytology)</term>
<term>Lymphocytes (cytology)</term>
<term>Mutation</term>
<term>Nuclear Receptor Subfamily 1, Group F, Member 3 (metabolism)</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Receptors, Antigen, T-Cell, gamma-delta (metabolism)</term>
<term>Receptors, Interleukin (metabolism)</term>
<term>Receptors, Interleukin-12 (metabolism)</term>
<term>Receptors, Interleukin-21 (metabolism)</term>
<term>STAT3 Transcription Factor (metabolism)</term>
<term>Signal Transduction</term>
<term>T-Lymphocytes (cytology)</term>
<term>Tumor Necrosis Factor-alpha (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Agranulocytes (cytologie)</term>
<term>Cellules tueuses naturelles (cytologie)</term>
<term>Cytokines (métabolisme)</term>
<term>Cytométrie en flux</term>
<term>Facteur de nécrose tumorale alpha (métabolisme)</term>
<term>Facteur de transcription STAT-3 (métabolisme)</term>
<term>Humains</term>
<term>Interféron gamma (métabolisme)</term>
<term>Interleukine-17 (métabolisme)</term>
<term>Interleukine-23 (métabolisme)</term>
<term>Interleukines (métabolisme)</term>
<term>Lymphocytes (cytologie)</term>
<term>Lymphocytes T (cytologie)</term>
<term>Membre-3 du groupe F de la sous-famille-1 de récepteurs nucléaires (métabolisme)</term>
<term>Mutation</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Récepteur lymphocytaire T antigène, gamma-delta (métabolisme)</term>
<term>Récepteurs aux interleukines (métabolisme)</term>
<term>Récepteurs à l'interleukine-12 (métabolisme)</term>
<term>Récepteurs à l'interleukine-21 (métabolisme)</term>
<term>Séparation cellulaire</term>
<term>Transduction du signal</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Cytokines</term>
<term>Interferon-gamma</term>
<term>Interleukin-17</term>
<term>Interleukin-23</term>
<term>Interleukins</term>
<term>Nuclear Receptor Subfamily 1, Group F, Member 3</term>
<term>Receptors, Antigen, T-Cell, gamma-delta</term>
<term>Receptors, Interleukin</term>
<term>Receptors, Interleukin-12</term>
<term>Receptors, Interleukin-21</term>
<term>STAT3 Transcription Factor</term>
<term>Tumor Necrosis Factor-alpha</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr">
<term>Agranulocytes</term>
<term>Cellules tueuses naturelles</term>
<term>Lymphocytes</term>
<term>Lymphocytes T</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en">
<term>Killer Cells, Natural</term>
<term>Leukocytes, Mononuclear</term>
<term>Lymphocytes</term>
<term>T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Cytokines</term>
<term>Facteur de nécrose tumorale alpha</term>
<term>Facteur de transcription STAT-3</term>
<term>Interféron gamma</term>
<term>Interleukine-17</term>
<term>Interleukine-23</term>
<term>Interleukines</term>
<term>Membre-3 du groupe F de la sous-famille-1 de récepteurs nucléaires</term>
<term>Récepteur lymphocytaire T antigène, gamma-delta</term>
<term>Récepteurs aux interleukines</term>
<term>Récepteurs à l'interleukine-12</term>
<term>Récepteurs à l'interleukine-21</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Cell Separation</term>
<term>Flow Cytometry</term>
<term>Humans</term>
<term>Mutation</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Cytométrie en flux</term>
<term>Humains</term>
<term>Mutation</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Séparation cellulaire</term>
<term>Transduction du signal</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Unconventional T cells such as γδ T cells, natural killer T cells (NKT cells) and mucosal-associated invariant T cells (MAIT cells) are a major component of the immune system; however, the cytokine signaling pathways that control their development and function in humans are unknown. Primary immunodeficiencies caused by single gene mutations provide a unique opportunity to investigate the role of specific molecules in regulating human lymphocyte development and function. We found that individuals with loss-of-function mutations in STAT3 had reduced numbers of peripheral blood MAIT and NKT but not γδ T cells. Analysis of STAT3 mosaic individuals revealed that this effect was cell intrinsic. Surprisingly, the residual STAT3-deficient MAIT cells expressed normal levels of the transcription factor RORγt. Despite this, they displayed a deficiency in secretion of IL-17A and IL-17F, but were able to secrete normal levels of cytokines such as IFNγ and TNF. The deficiency in MAIT and NKT cells in STAT3-deficient patients was mirrored by loss-of-function mutations in IL12RB1 and IL21R, respectively. Thus, these results reveal for the first time the essential role of STAT3 signaling downstream of IL-23R and IL-21R in controlling human MAIT and NKT cell numbers.</div>
</front>
</TEI>
</pubmed>
</double>
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