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

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

7 août 2015Science

Auteurs

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, Rubén Martinez-Barricarte, Chizuru Okada, Danielle T. Avery, Daniela Latorre, Caroline Deswarte, Fabienne Jabot-Hanin, Egidio Torrado, Jeffrey Fountain, Aziz Belkadi, Yuval Itan, Bertrand Boisson, Mélanie 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, Stéphanie Boisson-Dupuis, Anne Puel, Federica Sallusto, Jacinta Bustamante, Stuart G. Tangye, Jean-Laurent Casanova

Résumé

A surprising immune twist for RORC

The immune system needs its full array of soldiers—including cells and the molecules they secrete—to optimally protect the host. When this isn't the case, minor infections can become chronic or even deadly. Markle et al. report the discovery of seven individuals carrying loss-of-function mutations in RORC, which encodes the transcription factors RORγ and RORγT. These individuals lacked immune cells that produce the cytokine interleukin-17, causing them to suffer from chronic candidiasis. RORC-deficient individuals also exhibited impaired immunity to mycobacterium, probably due to reduced production of the cytokine interferon-γ, a molecule not known to require RORC for its induction.

Science , this issue p. 606

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