TGF-β limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function

M phi s promote tissue injury or repair depending on their activation status and the local cytokine milieu. It remains unclear whether the immunosuppressive effects of transforming growth factor beta (TGF-beta) serve a nonredundant role in M phi function in vivo. We generated M phi-specific transgenic mice that express a truncated TGF-beta receptor II under control of the CD68 promoter (CD68TGF-beta DNRII) and subjected these mice to the dextran sodium sulfate (DSS) model of colitis. CD68TGF-beta DNRII mice have an impaired ability to resolve colitic inflammation as demonstrated by increased lethality, granulocytic inflammation, and delayed goblet cell regeneration compared with transgene negative litter-mates. CD68TGF-beta DNRII mice produce significantly less IL-10, but have increased levels of IgE and numbers of IL-33(+) M phi s than controls. These data are consistent with associations between ulcerative colitis and increased IL-33 production in humans and suggest that TGF-beta may promote the suppression of intestinal inflammation, at least in part, through direct effects on M phi function.