title: TGF-β limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function.
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.
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Reena
authors.initials: R
authors.lastname: Rani
authors.forename: Alan G
authors.initials: AG
authors.lastname: Smulian
authors.forename: David R
authors.initials: DR
authors.lastname: Greaves
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hogan
authors.forename: De'Broski R
authors.initials: DR
authors.lastname: Herbert
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D015139:Blotting, Southern; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000276:immunology*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007073:Immunoglobulin E / Q000096:biosynthesis; D000067596:Interleukin-33; D007378:Interleukins / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016264:Dextran Sulfate; D007073:Immunoglobulin E; D000067596:Interleukin-33; D007378:Interleukins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C506535:Il33 protein, mouse