Induction and molecular signature of pathogenic T _H17 cells

Abstract

Interleukin 17 (IL-17)-producing T _H17 cells are often present at the sites of tissue inflammation in autoimmune diseases, which has lead to the conclusion that T _H17 are main drivers of autoimmune tissue injury. However, not all T _H17 cells are pathogenic, in fact T _H17 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 _H17 cells, is dependent on IL-23, which together with IL-6 induces highly pathogenic T _H17 cells. Moreover, TGF-β3-induced T _H17 cells are functionally and molecularly distinct from TGF-β1-induced T _H17 cells and possess a molecular signature that defines pathogenic effector T _H17 cells in autoimmune disease.