A nonredundant 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 a 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 it restricted IFNγ-induced proinflammatory genes. Our findings demonstrate spatiotemporal differences in the production and action of IL-22 by ILCs and T cells during infection and reveal an indispensable role for IL-22-producing T cells in the protection of the intestinal crypts.

TH17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity.

Acting in concert with TGF-ß, interleukin-6 (IL-6) signaling induces T helper 17 (TH17) cell development by programming TH17-related genes via signal transducers and activators of transcription 3 (STAT3). A role for IL-6 signaling beyond the inductive phase of TH17 cell development has not been defined because IL-23 signaling downstream of TH17 cell induction also activates STAT3 and is thought responsible for TH17 cell maintenance. Here, we find that IL-6 signaling is required for both induction and maintenance of mouse TH17 cells; IL-6Rα-deficient TH17 cells rapidly lost their TH17 phenotype and did not cause disease in two models of colitis. Cotransfer of wild-type TH17 cells with IL-6Rα-deficient TH17 cells induced colitis but was unable to rescue phenotype loss of the latter. High IL-6 expression in the colon promoted classic, or cis, rather than transreceptor signaling that was required for maintenance of TH17 cells. Thus, ongoing classic IL-6 signaling underpins the TH17 program and is required for TH17 cell maintenance and function.