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.
Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations / Okada, S., Markle, J.g., Deenick, E.k., Mele, F., Averbuch, D., Lagos, M., Alzahrani, M., Al-Muhsen, S., 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., Latorre, D., et al.. - In: SCIENCE. - ISSN 0036-8075. - 349:6248(2015), pp. 606-613. [10.1126/science.aaa4282]
Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations
Latorre D;
2015-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
