Interleukin 17 B is protective in colitis by regulating colonic mononuclear phagocytes in mice

IL17B protected mice from dextran sodium sulfate (DSS)-induced colitis since IL17B deficiency resulted in severe DSS-induced colitis with exaggerated weight loss, shorter colon length, and elevated proinflammatory cytokine production in colon. For mechanism study, we use single cell transcriptional analyses of CD45+ immune cells in colonic lamina propria to detect the effect of IL-17B on colon LP immune cells in colitis. We found increased inflammatory macrophages infiltration in colon lamina propria after colitis induction expressing inflammatory cytokines such as S100a9, S100a8, Tnf, which was confirmed by real-time PCR and flow cytometry. Reconstitute of Il17b-/- mice with recombinant IL17B alleviated the severity of DSS-induced colitis. IL17B treatment also inhibited LPS-induced inflammation in bone marrow derived macrophage and in mice. These data indicate that IL17B exerting its inhibitory role in inflammation by regulating inflammatory macrophage response. In view of the protective effect of IL17B on DSS-induced colitis and LPS-induced inflammation, IL17B might represent a novel potential therapeutic approach to treat the inflammation. Two WT and two Il17b-/- mice were fed with 2.5% (w/v) dextran sulfate sodium (DSS) for 6 days. The colon tissue was harvested from animals at day 9 and lamina proria cells were isolated to process single cell suspension for scRNAseq on BD Rhapsody system.