Editors' ChoiceImmunology

A surprising immune twist for RORC

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Sci. Signal.  11 Aug 2015:
Vol. 8, Issue 389, pp. ec227
DOI: 10.1126/scisignal.aad1987

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. Okada 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.

S. Okada, J. G. Markle, E. K. Deenick, F. Mele, D. Averbuch, M. Lagos, M. Alzahrani, S. Al-Muhsen, R. Halwani, C. S. Ma, N. Wong, C. Soudais, L. A. Henderson, H. Marzouqa, J. Shamma, M. Gonzalez, R. Martinez-Barricarte, C. Okada, D. T. Avery, D. Latorre, C. Deswarte, F. Jabot-Hanin, E. Torrado, J. Fountain, A. Belkadi, Y. Itan, B. Boisson, M. Migaud, C. S. Lindestam Arlehamn, A. Sette, S. Breton, J. McCluskey, J. Rossjohn, J.-P. de Villartay, D. Moshous, S. Hambleton, S. Latour, P. D. Arkwright, C. Picard, O. Lantz, D. Engelhard, M. Kobayashi, L. Abel, A. M. Cooper, L. D. Notarangelo, S. Boisson-Dupuis, A. Puel, F. Sallusto, J. Bustamante, S. G. Tangye, J.-L. Casanova, Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science 349, 606–613 (2015). [Abstract][Full Text]