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- Title
TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T<sub>H</sub>-17 cell–mediated pathology.
- Authors
McGeachy, Mandy J; Bak-Jensen, Kristian S; Chen, Yi; Tato, Cristina M; Blumenschein, Wendy; McClanahan, Terrill; Cua, Daniel J
- Abstract
Studies have shown that transforming growth factor-β (TGF-β) and interleukin 6 (IL-6) are required for the lineage commitment of pathogenic IL-17-producing T helper cells (TH-17 cells). Unexpectedly, here we found that stimulation of myelin-reactive T cells with TGF-β plus IL-6 completely abrogated their pathogenic function despite upregulation of IL-17 production. Cells stimulated with TGF-β plus IL-6 were present in the spleen as well as the central nervous system, but they failed to upregulate the proinflammatory chemokines crucial for central nervous system inflammation. In addition, these cells produced IL-10, which has potent anti-inflammatory activities. In contrast, stimulation with IL-23 promoted expression of IL-17 and proinflammatory chemokines but not IL-10. Hence, TGF-β and IL-6 'drive' initial lineage commitment but also 'restrain' the pathogenic potential of TH-17 cells. Our findings suggest that full acquisition of pathogenic function by effector TH-17 cells is mediated by IL-23 rather than by TGF-β and IL-6.
- Publication
Nature Immunology, 2007, Vol 8, Issue 12, p1390
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni1539