Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations

Satoshi Okada; Janet G. Markle; Elissa K. Deenick; Federico Mele; Dina Averbuch; Macarena Lagos; Mohammed Alzahrani; Saleh Al-Muhsen; Rabih Halwani; Cindy S. Ma; Natalie Wong; Claire Soudais; Lauren A. Henderson; Hiyam Marzouqa; Jamal Shamma; Marcela Gonzalez; Ruben Martinez-Barricarte; Chizuru Okada; Danielle T. Avery; Daniela Latorre; Caroline Deswarte; Fabienne Jabot-Hanin; Egidio Torrado; Jeffrey Fountain; Aziz Belkadi; Yuval Itan; Bertrand Boisson; Melanie Migaud; Cecilia S. Lindestam Arlehamn; Alessandro Sette; Sylvain Breton; James McCluskey; Jamie Rossjohn; Jean-Pierre de Villartay; Despina Moshous; Sophie Hambleton; Sylvain Latour; Peter D. Arkwright; Capucine Picard; Olivier Lantz; Dan Engelhard; Masao Kobayashi; Laurent Abel; Andrea M. Cooper; Luigi D. Notarangelo; Stephanie Boisson-Dupuis; Anne Puel; Federica Sallusto; Jacinta Bustamante; Stuart G. Tangye; Jean-Laurent Casanova

doi:10.1126/science.aaa4282

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Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations

Journal article

Peer reviewed

Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations

Satoshi Okada, Janet G. Markle, Elissa K. Deenick, Federico Mele, Dina Averbuch, Macarena Lagos, Mohammed Alzahrani, Saleh Al-Muhsen, Rabih Halwani, Cindy S. Ma, …

Science (American Association for the Advancement of Science), Vol.349(6248), pp.606-613

07/08/2015

DOI: https://doi.org/10.1126/science.aaa4282

PMCID: PMC4668938

PMID: 26160376

Abstract

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

Human inborn errors of immunity mediated by the cytokines interleukin-17A and interleukin-17F (IL-17A/F) underlie mucocutaneous candidiasis, whereas inborn errors of interferon-gamma (IFN-gamma) immunity underlie mycobacterial disease. We report the discovery of bi-allelic RORC loss-of-function mutations in seven individuals from three kindreds of different ethnic origins with both candidiasis and mycobacteriosis. The lack of functional ROR gamma and ROR gamma T isoforms resulted in the absence of IL-17A/F-producing T cells in these individuals, probably accounting for their chronic candidiasis. Unexpectedly, leukocytes from ROR gamma- and ROR gamma T-deficient individuals also displayed an impaired IFN-gamma response to Mycobacterium. This principally reflected profoundly defective IFN-gamma production by circulating gamma delta T cells and CD4+CCR6+CXCR3+ alpha beta T cells. In humans, both mucocutaneous immunity to Candida and systemic immunity to Mycobacterium require ROR gamma, ROR gamma T, or both.

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Title: Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations
Creators - without role: Satoshi Okada - Rockefeller University
Janet G. Markle - Rockefeller University
Elissa K. Deenick - Garvan Institute of Medical Research
Federico Mele - Università della Svizzera italiana
Dina Averbuch - Hadassah Academic College
Macarena Lagos - University of Valparaíso
Mohammed Alzahrani - King Faisal Specialist Hospital & Research Centre
Saleh Al-Muhsen - King Saud University
Rabih Halwani - King Saud University
Cindy S. Ma - UNSW Sydney
Natalie Wong - Garvan Institute of Medical Research
Claire Soudais - Institute Curie
Lauren A. Henderson - Boston Children's Hospital
Hiyam Marzouqa - Catholic Development Office
Jamal Shamma - Catholic Development Office
Marcela Gonzalez - University of Valparaíso
Ruben Martinez-Barricarte - Rockefeller University
Chizuru Okada - Rockefeller University
Danielle T. Avery - Garvan Institute of Medical Research
Daniela Latorre - Univ Italian Switzerland, Inst Res Biomed, Bellinzona, Switzerland
Caroline Deswarte - Imagine Institute for Genetic Diseases
Fabienne Jabot-Hanin - Inserm
Egidio Torrado - Trudeau Institute
Jeffrey Fountain - Trudeau Institute
Aziz Belkadi - Inserm
Yuval Itan - Rockefeller University
Bertrand Boisson - Rockefeller University
Melanie Migaud - Inserm
Cecilia S. Lindestam Arlehamn - La Jolla Institute For Allergy & Immunology
Alessandro Sette - La Jolla Institute For Allergy & Immunology
Sylvain Breton - Assistance Publique – Hôpitaux de Paris
James McCluskey - Peter Doherty Institute
Jamie Rossjohn - Monash University
Jean-Pierre de Villartay - Délégation Paris 5
Despina Moshous - Délégation Paris 5
Sophie Hambleton - Great North Children's Hospital
Sylvain Latour - Sorbonne Paris Cité
Peter D. Arkwright - Royal Manchester Children's Hospital
Capucine Picard - Inserm
Olivier Lantz - Institute Curie
Dan Engelhard - Hadassah Academic College
Masao Kobayashi - Hiroshima University
Laurent Abel - Rockefeller University
Andrea M. Cooper - Trudeau Institute
Luigi D. Notarangelo - Boston Children's Hospital
Stephanie Boisson-Dupuis - Inserm
Anne Puel - Rockefeller University
Federica Sallusto - Università della Svizzera italiana
Jacinta Bustamante - Rockefeller University
Stuart G. Tangye - St Vincent's Clinic
Jean-Laurent Casanova - Rockefeller University
Publication Details: Science (American Association for the Advancement of Science), Vol.349(6248), pp.606-613
Publisher: Amer Assoc Advancement Science
Number of pages: 8
Grant note: Rockefeller University INSERM; Institut National de la Sante et de la Recherche Medicale (Inserm) St. Giles Foundation 25713039; 25670477 / Japan Society for the Promotion of Science; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) R37AI095983 / National Institute of Allergy and Infectious Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Laboratory of Human Genetics of Infectious Diseases 149475 / Swiss National Science Foundation; Swiss National Science Foundation (SNSF) ANR-10-IAHU-01; 13-ISV3-0001-01; 11-BSV3-005-01 / French National Research Agency (ANR); Agence Nationale de la Recherche (ANR); Norwegian Agency for Development Cooperation - NORAD ANR-10-LABX-62-IBEID / Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases Universite Paris Descartes European Molecular Biology Organization; European Molecular Biology Organization (EMBO) Rheumatology Research Foundation's Scientist Development Award 8UL1TR000043 / National Center for Advancing Sciences, NIH HHSN272200900044C / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 323183 PREDICT / European Research Council; European Research Council (ERC); European Commission 12JTA / The Sir Jules Thorn Charitable Trust 25713039; 25670477 / Grants-in-Aid for Scientific Research; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT); Japan Society for the Promotion of Science; Grants-in-Aid for Scientific Research (KAKENHI) National Center for Research Resources, NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) National Health and Medical Research Council (NHMRC); National Health and Medical Research Council (NHMRC) of Australia Canadian Institutes of Health Research; Canadian Institutes of Health Research (CIHR) AXA Research Fund Helmut Horten Foundation
Identifiers: 9949898008331
Academic Unit: King Saud University
Language: English
Resource Type: Journal article