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

ABSTRACT: M?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 ? (TGF-?) serve a nonredundant role in M? function in vivo. We generated M?-specific transgenic mice that express a truncated TGF-? receptor II under control of the CD68 promoter (CD68TGF-?DNRII) and subjected these mice to the dextran sodium sulfate (DSS) model of colitis. CD68TGF-?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-?DNRII mice produce significantly less IL-10, but have increased levels of IgE and numbers of IL-33+ M?s than controls. These data are consistent with associations between ulcerative colitis and increased IL-33 production in humans and suggest that TGF-? may promote the suppression of intestinal inflammation, at least in part, through direct effects on M? function.

SUBMITTER: Rani R 

PROVIDER: S-EPMC3139176 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature