title: Critical roles of TIPE2 protein in murine experimental colitis.
abstract: Both commensal bacteria and infiltrating inflammatory cells play essential roles in the pathogenesis of inflammatory bowel disease. The molecular mechanisms whereby these pathogenic factors are regulated during the disease are not fully understood. We report in this article that a member of the TNF-α-induced protein 8 (TNFAIP8) family called TIPE2 (TNFAIP8-like 2) plays a crucial role in regulating commensal bacteria dissemination and inflammatory cell function in experimental colitis induced by dextran sodium sulfate (DSS). Following DSS treatment, TIPE2-deficient mice, or chimeric mice that are deficient in TIPE2 only in their hematopoietic cells, lost less body weight and survived longer than wild-type controls. Consistent with this clinical observation, TIPE2-deficient mice exhibited significantly less severe colitis and colonic damage. This was associated with a marked reduction in the colonic expression of inflammatory cytokines, such as TNF-α, IL-6, and IL-12. Importantly, the ameliorated DSS-induced colitis in TIPE2(-/-) mice also was associated with reduced local dissemination of commensal bacteria and a weaker systemic inflammatory response. Combined with our previous report that TIPE2 is a negative regulator of antibacterial immunity, these results indicate that TIPE2 promotes colitis by inhibiting mucosal immunity to commensal bacteria.
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104; Department of Immunology, Shandong University School of Medicine, Ji'nan 250012, People's Republic of China; and.
authors: Yunwei
authors: Y
authors: Lou
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104;
authors: Honghong
authors: H
authors: Sun
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104;
authors: Samantha
authors: S
authors: Morrissey
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104;
authors: Thomas
authors: T
authors: Porturas
authors: Department of Immunology, Shandong University School of Medicine, Ji'nan 250012, People's Republic of China; and.
authors: Suxia
authors: S
authors: Liu
authors: Department of Cancer Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104.
authors: Xianxin
authors: X
authors: Hua
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104; yhc@mail.med.upenn.edu.
authors: Youhai H
authors: YH
authors: Chen
mesh_terms: D000818:Animals; D001419:Bacteria / Q000235:genetics; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011828:Radiation Chimera; D013431:Sulfates / Q000633:toxicity
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D013431:Sulfates; C529002:TIPE2 protein, mouse; C012036:sodium sulfate