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 Zaid 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

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 Zaid 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 LatorreCaroline 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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › Research › peer-review

366 Citations (Scopus)

Abstract

Human inborn errors of immunity mediated by the cytokines interleukin-17A/F (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 RORgamma and RORgammaT isoforms resulted in the absence of IL-17A/F-producing T cells in these individuals, probably accounting for their chronic candidiasis. Unexpectedly, leukocytes from RORgamma- and RORgammaT-deficient individuals also displayed an impaired IFN-gamma response to Mycobacterium. This principally reflected profoundly defective IFN-gamma production by circulating gammadelta T cells and CD4+CCR6+CXCR3+ alphabeta T cells. In humans, both mucocutaneous immunity to Candida and systemic immunity to Mycobacterium require RORgamma, or RORgammaT, or both.

Original language	English
Pages (from-to)	606 - 613
Number of pages	8
Journal	Science
Volume	349
Issue number	6248
DOIs	https://doi.org/10.1126/science.aaa4282
Publication status	Published - 2015

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Okada, S., Markle, J. G., Deenick, E. K., Mele, F., Averbuch, D., Lagos, M., Alzahrani, M., Al-Muhsen, S. Z., Halwani, R., Ma, C. S., Wong, N., Soudais, C., Henderson, L. A., Marzouqa, H., Shamma, J., Gonzalez, M., Martinez-Barricarte, R., Okada, C., Avery, D. T., ... Casanova, J.-L. (2015). Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science, 349(6248), 606 - 613. https://doi.org/10.1126/science.aaa4282

@article{0c355a762b4d487d98e8f3039a056741,

title = "Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations",

abstract = "Human inborn errors of immunity mediated by the cytokines interleukin-17A/F (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 RORgamma and RORgammaT isoforms resulted in the absence of IL-17A/F-producing T cells in these individuals, probably accounting for their chronic candidiasis. Unexpectedly, leukocytes from RORgamma- and RORgammaT-deficient individuals also displayed an impaired IFN-gamma response to Mycobacterium. This principally reflected profoundly defective IFN-gamma production by circulating gammadelta T cells and CD4+CCR6+CXCR3+ alphabeta T cells. In humans, both mucocutaneous immunity to Candida and systemic immunity to Mycobacterium require RORgamma, or RORgammaT, or both.",

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

year = "2015",

doi = "10.1126/science.aaa4282",

language = "English",

volume = "349",

pages = "606 -- 613",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science (AAAS)",

number = "6248",

}

Okada, S, Markle, JG, Deenick, EK, Mele, F, Averbuch, D, Lagos, M, Alzahrani, M, Al-Muhsen, SZ, Halwani, R, Ma, CS, Wong, N, Soudais, C, Henderson, LA, Marzouqa, H, Shamma, J, Gonzalez, M, Martinez-Barricarte, R, Okada, C, Avery, DT, Latorre, D, Deswarte, C, Jabot-Hanin, F, Torrado, E, Fountain, J, Belkadi, A, Itan, Y, Boisson, B, Migaud, M, Arlehamn, CSL, Sette, A, Breton, S, McCluskey, J, Rossjohn, J, de Villartay, J-P, Moshous, D, Hambleton, S, Latour, S, Arkwright, PD, Picard, C, Lantz, O, Engelhard, D, Kobayashi, M, Abel, L, Cooper, AM, Notarangelo, LD, Boisson-Dupuis, S, Puel, A, Sallusto, F, Bustamante, J, Tangye, SG & Casanova, J-L 2015, 'Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations', Science, vol. 349, no. 6248, pp. 606 - 613. https://doi.org/10.1126/science.aaa4282

TY - JOUR

T1 - Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations

AU - Okada, Satoshi

AU - Markle, Janet G

AU - Deenick, Elissa K

AU - Mele, Federico

AU - Averbuch, Dina

AU - Lagos, Macarena

AU - Alzahrani, Mohammed

AU - Al-Muhsen, Saleh Zaid

AU - Halwani, Rabih

AU - Ma, Cindy S

AU - Wong, Natalie

AU - Soudais, Claire

AU - Henderson, Lauren A

AU - Marzouqa, Hiyam

AU - Shamma, Jamal

AU - Gonzalez, Marcela

AU - Martinez-Barricarte, Ruben

AU - Okada, Chizuru

AU - Avery, Danielle T

AU - Latorre, Daniela

AU - Deswarte, Caroline

AU - Jabot-Hanin, Fabienne

AU - Torrado, Egidio

AU - Fountain, Jeffrey

AU - Belkadi, Aziz

AU - Itan, Yuval

AU - Boisson, Bertrand

AU - Migaud, Melanie

AU - Arlehamn, Cecilia S Lindestam

AU - Sette, Alessandro

AU - Breton, Sylvain

AU - McCluskey, James

AU - Rossjohn, Jamie

AU - de Villartay, Jean-Pierre

AU - Moshous, Despina

AU - Hambleton, Sophie

AU - Latour, Sylvain

AU - Arkwright, Peter D

AU - Picard, Capucine

AU - Lantz, Olivier

AU - Engelhard, Dan

AU - Kobayashi, Masao

AU - Abel, Laurent

AU - Cooper, Andrea M

AU - Notarangelo, Luigi D

AU - Boisson-Dupuis, Stephanie

AU - Puel, Anne

AU - Sallusto, Federica

AU - Bustamante, Jacinta

AU - Tangye, Stuart G

AU - Casanova, Jean-Laurent

PY - 2015

Y1 - 2015

N2 - Human inborn errors of immunity mediated by the cytokines interleukin-17A/F (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 RORgamma and RORgammaT isoforms resulted in the absence of IL-17A/F-producing T cells in these individuals, probably accounting for their chronic candidiasis. Unexpectedly, leukocytes from RORgamma- and RORgammaT-deficient individuals also displayed an impaired IFN-gamma response to Mycobacterium. This principally reflected profoundly defective IFN-gamma production by circulating gammadelta T cells and CD4+CCR6+CXCR3+ alphabeta T cells. In humans, both mucocutaneous immunity to Candida and systemic immunity to Mycobacterium require RORgamma, or RORgammaT, or both.

AB - Human inborn errors of immunity mediated by the cytokines interleukin-17A/F (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 RORgamma and RORgammaT isoforms resulted in the absence of IL-17A/F-producing T cells in these individuals, probably accounting for their chronic candidiasis. Unexpectedly, leukocytes from RORgamma- and RORgammaT-deficient individuals also displayed an impaired IFN-gamma response to Mycobacterium. This principally reflected profoundly defective IFN-gamma production by circulating gammadelta T cells and CD4+CCR6+CXCR3+ alphabeta T cells. In humans, both mucocutaneous immunity to Candida and systemic immunity to Mycobacterium require RORgamma, or RORgammaT, or both.

UR - http://www.ncbi.nlm.nih.gov/pubmed/26160376

U2 - 10.1126/science.aaa4282

DO - 10.1126/science.aaa4282

M3 - Article

SN - 0036-8075

VL - 349

SP - 606

EP - 613

JO - Science

JF - Science

IS - 6248

ER -

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

Abstract

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