TGF-beta signaling on dendritic cells regulates bacterial communities and gut homeostasis

BACKGROUND: Dendritic cells (DCs) are essential mediators of immune responses and gut homeostasis. We investigated the involvement of TGF-beta signaling on DCs in the regulation of colitis and gut microbiota. METHODS: We used DC specific TGFBRII-deficient mice (KO; CD11c-cre Tgfbr2 fl/fl, HT; CD11c-cre Tgfbr2 fl/+), and wild type (WT) mice. WT and HT mice received DSS with or without antibiotics. DNA was extracted from feces of each mouse and qPCR of bacterial 16s rRNA gene was analyzed. Fecal microbiota transplantation (FMT) was performed from WT or KO mice orogastrically to antibiotics-pretreated WT mice. RESULTS: KO mice died early weeks of age with spontaneous colitis. HT mice were more susceptible to DSS-induced colitis than WT mice. In contrast, WT and HT mice with DSS plus antibiotics did not exhibit colitis. Analysis of 16s rRNA gene showed Enterobacteriaceae were enriched in KO mice and DSS-induced HT mice compared to that in WT mice. In contrast, the abundance of Enterobacteriaceae did not differ between WT and HT mice with DSS plus antibiotics. In FMT, mice gavaged with feces from KO mice were more susceptible to colitis than from WT mice. CONCLUSIONS: DC specific TGFBRII-deficient mice are more susceptible to colitis, partly due to dysbiosis. Our results indicate that genetic and microbial factors affect each other in the pathogenesis of IBD.