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 CD8αα+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 CD8αα+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 CD8αα+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.
Gut epithelial IL-27 confers intestinal immunity through the induction of intraepithelial lymphocytes
Disclosures: L.-F. Lu is a scientific advisor for Elixiron Immunotherapeutics. No other disclosures were reported.
- Award Id(s): AI108651,AI127751,AI163813,AI125247
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Chia-Hao Lin, Mei-Chi Chen, Ling-Li Lin, David A. Christian, Booki Min, Christopher A. Hunter, Li-Fan Lu; Gut epithelial IL-27 confers intestinal immunity through the induction of intraepithelial lymphocytes. J Exp Med 1 November 2021; 218 (11): e20210021. doi: https://doi.org/10.1084/jem.20210021
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