TGF‐β limits IL‐33 production and promotes the resolution of colitis through regulation of macrophage function
Open Access
- 6 April 2011
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 41 (7), 2000-2009
- https://doi.org/10.1002/eji.201041135
Abstract
Mϕs 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 β (TGF‐β) serve a nonredundant role in Mϕ function in vivo. We generated Mϕ‐specific transgenic mice that express a truncated TGF‐β receptor II under control of the CD68 promoter (CD68TGF‐βDNRII) and subjected these mice to the dextran sodium sulfate (DSS) model of colitis. CD68TGF‐βDNRII 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‐βDNRII mice produce significantly less IL‐10, but have increased levels of IgE and numbers of IL‐33+ Mϕs than controls. These data are consistent with associations between ulcerative colitis and increased IL‐33 production in humans and suggest that TGF‐β may promote the suppression of intestinal inflammation, at least in part, through direct effects on Mϕ function.Keywords
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