A Non-redundant Role for T cell-derived Interleukin 22 in Antibacterial Defense of Colonic Crypts

Interleukin (IL)-22 is central to immune defense at barrier sites. We examined the contributions of innate lymphoid cell (ILC) and T cell-derived IL-22 during Citrobacter rodentium (C.r) infection using mice that both report Il22 expression and allow lineage-specific deletion. ILC-derived IL-22 activated STAT3 in C.r -colonized surface intestinal epithelial cells (IECs), but only temporally restrained bacterial growth. T cell-derived IL-22 induced more robust and extensive activation of STAT3 in IECs, including IECs lining colonic crypts, and T cell-specific deficiency of IL-22 led to pathogen invasion of the crypts and increased mortality. This reflected a requirement for T cell-derived IL-22 for the expression of a host-protective transcriptomic program that included AMPs, neutrophil-recruiting chemokines and mucin-related molecules, and restricted IFNγ–induced pro-inflammatory genes. Our findings demonstrate spatiotemporal differences in the production and action of IL-22 by ILCs and T cells during infection and reveal an indispenable role for IL-22–producing T cells in the protection of the intestinal crypts. Interleukin (IL)-22–producing innate and adaptive immune cells contribute to host protection at barrier sites. Zindl et al. reveal that IL-22 + ILCs and T cells are specialized for early versus late protection of the intestinal mucosa via distinct patterns of activation of intestinal epithelial cells: actions of ILCs are limited to the superficial IECs to limit early bacterial colonization whereas, IL-22 + CD4 T cells recruited to the LP uniquely target crypt IECs to restrain bacterial spread into the colonic crypts.