Thymic self-reactivity selects natural interleukin 17-producing T cells that can regulate peripheral inflammation

Interleukin 17 (IL-17)-producing CD4(+) T (T(H)-17) cells share a developmental relationship with FoxP3(+) regulatory T (T(reg)) cells. Here we show that a T(H)-17 population differentiates within the thymus in a manner influenced by self-antigen recognition, and by the cytokines IL-6 and transforming growth factor (TGF)-β. Like previously described T(H)-17 cells, T(H)-17 cells that develop in the thymus expressed the orphan nuclear receptor RORγt and the IL-23 receptor. These cells also expressed α4β1 integrins and the chemokine receptor CCR6, and were recruited to the lung, gut, and liver. In the liver these cells secreted IL-22 in response to self-antigen and mediated host protection during inflammation. Thus, T(H)-17 cells, like T(reg) cells, can be selected by self-antigens in the thymus.