Gut epithelial IL-27 confers intestinal immunity through the induction of intraepithelial lymphocytes

IL-27 controls a diverse range of immune responses in many disease settings. Here, we identify intestinal epithelial cells (IECs) as one of the major IL-27 cellular sources in the gut-associated tissue. Unlike IL-27 secreted by innate immune cells, gut epithelial IL-27 is dispensable for T-bet' regulatory T cell (T reg cell) differentiation or IL-10 induction. Rather, IEC-derived IL-27 specifically promotes a distinct CD8 alpha alpha'CD4' intraepithelial lymphocyte (IEL) population that acquires their functional differentiation at the intestinal epithelium. Loss of IL-27 in IECs leads to a selective defect in CD8 alpha alpha'CD4' IELs over time. Consequently, mice with IEC-specific IL-27 ablation exhibited elevated pathogen burden during parasitic infection, and this could be rescued by transfer of exogenous CD8 alpha alpha'CD4' IELs. Collectively, our data reveal that in addition to its known regulatory properties in preventing immune hyperactivity, gut epithelial IL-27 confers barrier immunity by inducing a specific IEL subset and further suggest that IL-27 produced by different cell types plays distinct roles in maintaining intestinal homeostasis.

Automated summary

IL-27 produced by intestinal epithelial cells plays a crucial role in promoting a specific subset of intraepithelial lymphocytes, contributing to barrier immunity in the gut. Loss of IL-27 in IECs leads to a selective defect in certain IEL populations, resulting in elevated pathogen burden during parasitic infection. This suggests that IL-27 from different cell types plays distinct roles in maintaining intestinal homeostasis.