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

Ms 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 function in vivo. We generated M-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 littermates. CD68TGF-[beta]DNRII mice produce significantly less IL-10, but have increased levels of IgE and numbers of IL-33+ Ms 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 function. [PUBLICATION ABSTRACT]