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

Abstract

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 TH-17 cells to the list of T cell subsets enriched by self-reactivity. Interleukin 17 (IL-17)-producing CD4+ helper T cells (TH-17 cells) share a developmental relationship with Foxp3+ regulatory T cells (Treg cells). Here we show that a TH-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 TH-17 cells, the TH-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, TH-17 cells, like Treg cells, can be selected by self antigens in the thymus.