Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of T17 cell immunity.

Regulatory T cells (T cells) are instrumental in establishing immunological tolerance. However, the precise effector mechanisms by which T cells control a specific type of immune response in a given tissue remains unresolved. By simultaneously studying T cells from different tissue origins under systemic autoimmunity, in the present study we show that interleukin (IL)-27 is specifically produced by intestinal T cells to regulate helper T17 cell (T17 cell) immunity. Selectively increased intestinal T17 cell responses in mice with T cell-specific IL-27 ablation led to exacerbated intestinal inflammation and colitis-associated cancer, but also helped protect against enteric bacterial infection. Furthermore, single-cell transcriptomic analysis has identified a CD83CD62L T cell subset that is distinct from previously characterized intestinal T cell populations as the main IL-27 producers. Collectively, our study uncovers a new T cell suppression mechanism crucial for controlling a specific type of immune response in a particular tissue and provides further mechanistic insights into tissue-specific T cell-mediated immune regulation.