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

Several unconventional T cell populations, including γδ T cells and regulatory T cells, are selected by recognition of self antigen in the thymus. Craft and colleagues add T H -17 cells to the list of T cell subsets enriched by self-reactivity. 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 α 4 β 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.