2015年8月
Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations
SCIENCE
- 巻
- 349
- 号
- 6248
- 開始ページ
- 606
- 終了ページ
- 613
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1126/science.aaa4282
- 出版者・発行元
- AMER ASSOC ADVANCEMENT SCIENCE
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.
- リンク情報
-
- DOI
- https://doi.org/10.1126/science.aaa4282
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201502213600823241
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/26160376
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000359092900033&DestApp=WOS_CPL
- URL
- http://orcid.org/0000-0002-4622-5657
- ID情報
-
- DOI : 10.1126/science.aaa4282
- ISSN : 0036-8075
- eISSN : 1095-9203
- J-Global ID : 201502213600823241
- ORCIDのPut Code : 19693385
- PubMed ID : 26160376
- Web of Science ID : WOS:000359092900033