Induction and molecular signature of pathogenic T(H)17 cells

Interleukin 17 (IL-17)-producing T(H)17 cells are often present at the sites of tissue inflammation in autoimmune diseases, which has lead to the conclusion that T(H)17 are main drivers of autoimmune tissue injury. However, not all T(H)17 cells are pathogenic, in fact T(H)17 generated with TGF-β1 and IL-6 produce IL-17 but do not readily induce autoimmune disease without further exposure to IL-23. Here we show that TGF-β3, produced by developing T(H)17 cells, is dependent on IL-23, which together with IL-6 induces highly pathogenic T(H)17 cells. Moreover, TGF-β3-induced T(H)17 cells are functionally and molecularly distinct from TGF-β1-induced T(H)17 cells and possess a molecular signature that defines pathogenic effector T(H)17 cells in autoimmune disease.