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- Title
IL-21 and TGF-β are required for differentiation of human T<sub>H</sub>17 cells.
- Authors
Yang, Li; Anderson, David E.; Baecher-Allan, Clare; Hastings, William D.; Bettelli, Estelle; Oukka, Mohamed; Kuchroo, Vijay K.; Hafler, David A.
- Abstract
The recent discovery of CD4+ T cells characterized by secretion of interleukin (IL)-17 (TH17 cells) and the naturally occurring regulatory FOXP3+ CD4 T cell (nTreg) has had a major impact on our understanding of immune processes not readily explained by the TH1/TH2 paradigm. TH17 and nTreg cells have been implicated in the pathogenesis of human autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and psoriasis. Our recent data and the work of others demonstrated that transforming growth factor-β (TGF-β) and IL-6 are responsible for the differentiation of naive mouse T cells into TH17 cells, and it has been proposed that IL-23 may have a critical role in stabilization of the TH17 phenotype. A second pathway has been discovered in which a combination of TGF-β and IL-21 is capable of inducing differentiation of mouse TH17 cells in the absence of IL-6 (refs 6–8). However, TGF-β and IL-6 are not capable of differentiating human TH17 cells and it has been suggested that TGF-β may in fact suppress the generation of human TH17 cells. Instead, it has been recently shown that the cytokines IL-1β, IL-6 and IL-23 are capable of driving IL-17 secretion in short-term CD4+ T cell lines isolated from human peripheral blood, although the factors required for differentiation of naive human CD4 to TH17 cells are still unknown. Here we confirm that whereas IL-1β and IL-6 induce IL-17A secretion from human central memory CD4+ T cells, TGF-β and IL-21 uniquely promote the differentiation of human naive CD4+ T cells into TH17 cells accompanied by expression of the transcription factor RORC2. These data will allow the investigation of this new population of TH17 cells in human inflammatory disease.
- Subjects
IMMUNOLOGY; CD4 antigen; T cells; TRANSFORMING growth factors-beta; AUTOIMMUNE diseases; INTERLEUKINS; CYTOKINES
- Publication
Nature, 2008, Vol 454, Issue 7202, p350
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature07021