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

Interleukin 17 (IL-17)-producing CD4(+) helper T cells (T-H-17 cells) share a developmental relationship with Foxp3(+) regulatory T cells (T-reg cells). Here we show that a T-H-17 population differentiates in the thymus in a manner influenced by recognition of self antigen and by the cytokines IL-6 and transforming growth factor-beta (TGF-beta). Like previously described T-H-17 cells, the T-H-17 cells that developed in the thymus expressed the transcription factor ROR gamma t and the IL-23 receptor. These cells also expressed alpha(4)beta(1) 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.