title: Thrombospondin 1 Modulates Monocyte Properties to Suppress Intestinal Mucosal Inflammation.
abstract: Monocytes (Mos) play an important role in the pathogenesis of intestinal mucosal inflammation. This study aims to investigate the mechanism by which the intestinal epithelial cell-derived thrombospondin 1 (TSP1) modulates Mo properties and regulates intestinal inflammatory responses. In this study, the production of TSP1 by intestinal epithelial cells was evaluated by quantitative real-time PCR and Western blotting. The properties of Mos were analyzed by flow cytometry. A mouse model of colitis was created to assess the role of epithelium-derived TSP1 in the suppression of intestinal inflammation. The results demonstrated that mouse intestinal epithelial cells (IECs) expressed TSP1, which was markedly upregulated by butyrate or feeding with Clostridium butyricum. Coculture of the butyrate-primed IECs and Mos or exposure of Mos to TSP1 in the culture induced the expression of transforming growth factor (TGF)-β in Mos. These TGF-β+ Mos had tolerogenic properties that could promote generation of inducible regulatory T cells. Adoptive transfer with TSP1-primed Mos, or feeding C. butyricum could prevent experimental colitis in mice. In summary, C. butyricum induces intestinal epithelial cells to produce TSP1 and induces TGF-β+ Mos, which further suppress experimental colitis in mice. The results implicate that the administration of C. butyricum or butyrate may have the potential to ameliorate chronic intestinal inflammation through inducing immunosuppressive Mos.
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Fang
authors.forename: Hai-Qiong
authors.initials: HQ
authors.lastname: Yu
authors.forename: Rui-Jin
authors.initials: RJ
authors.lastname: Wu
authors.forename: Chong
authors.initials: C
authors.lastname: He
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Yan
authors.forename: Jian-Jie
authors.initials: JJ
authors.lastname: Li
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Liu
authors.forename: Zhan-Ju
authors.initials: ZJ
authors.lastname: Liu
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000818:Animals; D002087:Butyrates / Q000633:toxicity; D046972:Clostridium butyricum / Q000276:immunology; D003092:Colitis / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D019700:Thrombospondin 1 / Q000235:genetics / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology
chemical_list: D002087:Butyrates; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta