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

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

in Accounting / Bacteria / Candida / Cytokines / Errors / Immune system / Immune systems / Immunity / Interleukin / Mutation / Mutations / Mycobacterium / Yeast

2015

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

in Accounting / Bacteria / Candida / Cytokines / Errors / Immune system / Immune systems / Immunity / Interleukin / Mutation / Mutations / Mycobacterium / Yeast

2015

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

in Accounting / Bacteria / Candida / Cytokines / Errors / Immune system / Immune systems / Immunity / Interleukin / Mutation / Mutations / Mycobacterium / Yeast

2015

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Journal Article

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

Wong, Natalie,

Moshous, Despina,

Latour, Sylvain,

Tangye, Stuart G.,

Sette, Alessandro,

Okada, Satoshi,

Fountain, Jeffrey,

Sallusto, Federica,

Kobayashi, Masao,

Hambleton, Sophie,

Boisson, Bertrand,

Henderson, Lauren A.,

Deswarte, Caroline,

Engelhard, Dan,

Bustamante, Jacinta,

Ma, Cindy S.,

Breton, Sylvain,

de Villartay, Jean-Pierre,

Shamma, Jamal,

Soudais, Claire,

Rossjohn, Jamie,

Boisson-Dupuis, Stéphanie,

Okada, Chizuru,

Deenick, Elissa K.,

Cooper, Andrea M.,

Lagos, Macarena,

Avery, Danielle T.,

McCluskey, James,

Itan, Yuval,

Torrado, Egidio,

Migaud, Mélanie,

Belkadi, Aziz,

Averbuch, Dina,

Halwani, Rabih,

Latorre, Daniela,

Marzouqa, Hiyam,

Arkwright, Peter D.,

Gonzalez, Marcela,

Martinez-Barricarte, Rubén,

Markle, Janet G.,

Notarangelo, Luigi D.,

Al-Muhsen, Saleh,

Lantz, Olivier,

Puel, Anne,

Jabot-Hanin, Fabienne,

Arlehamn, Cecilia S. Lindestam,

Abel, Laurent,

Casanova, Jean-Laurent,

Mele, Federico,

Picard, Capucine,

Alzahrani, Mohammed

2015

Overview

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-γ (IFN-γ) 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 RORγ and RORγT isoforms resulted in the absence of IL-17A/F–producing T cells in these individuals, probably accounting for their chronic candidiasis. Unexpectedly, leukocytes from RORγ- and RORγT-deficient individuals also displayed an impaired IFN-γ response to Mycobacterium. This principally reflected profoundly defective IFN-γ production by circulating γδ T cells and CD4+CCR6+CXCR3+ αβ T cells. In humans, both mucocutaneous immunity to Candida and systemic immunity to Mycobacterium require RORγ, RORγT, or both.

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Publisher

American Association for the Advancement of Science,The American Association for the Advancement of Science

Subject

/ Candida

/ Errors