Article abstract
Nature Immunology 8, 1390 - 1397 (2007)
Published online: 11 November 2007 | doi:10.1038/ni1539
TGF-
and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell–mediated pathology
Mandy J McGeachy1, Kristian S Bak-Jensen1, Yi Chen1, Cristina M Tato1, Wendy Blumenschein1, Terrill McClanahan1 & Daniel J Cua1
Abstract
Studies have shown that transforming growth factor-
(TGF-) 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- plus IL-6 completely abrogated their pathogenic function despite upregulation of IL-17 production. Cells stimulated with TGF- 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- 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- and IL-6.
- Schering-Plough Biopharma, Palo Alto, California 94304, USA.
Correspondence to: Daniel J Cua1 e-mail: daniel.cua@dnax.org
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