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-β (TGF-β). Like previously described T_H-17 cells, the T_H-17 cells that developed in the thymus expressed the transcription factor 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. [ABSTRACT FROM AUTHOR]