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Nat Immunol. 2012 Oct;13(10):991-9. doi: 10.1038/ni.2416. Epub 2012 Sep 9.

Induction and molecular signature of pathogenic TH17 cells.

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1
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

Interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) are often present at the sites of tissue inflammation in autoimmune diseases, which has led to the conclusion that T(H)17 cells are main drivers of autoimmune tissue injury. However, not all T(H)17 cells are pathogenic; in fact, T(H)17 cells generated with transforming growth factor-β1 (TGF-β1) and IL-6 produce IL-17 but do not readily induce autoimmune disease without further exposure to IL-23. Here we found that the production of TGF-β3 by developing T(H)17 cells was dependent on IL-23, which together with IL-6 induced very pathogenic T(H)17 cells. Moreover, TGF-β3-induced T(H)17 cells were functionally and molecularly distinct from TGF-β1-induced T(H)17 cells and had a molecular signature that defined pathogenic effector T(H)17 cells in autoimmune disease.

PMID:
22961052
PMCID:
PMC3459594
DOI:
10.1038/ni.2416
[Indexed for MEDLINE]
Free PMC Article

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