title: Impaired removal of Vβ8(+) lymphocytes aggravates colitis in mice deficient for B cell lymphoma-2-interacting mediator of cell death (Bim).
abstract: We investigated the role of B cell lymphoma (BCL)-2-interacting mediator of cell death (Bim) for lymphocyte homeostasis in intestinal mucosa. Lymphocytes lacking Bim are refractory to apoptosis. Chronic colitis was induced in Bim-deficient mice (Bim(-/-) ) with dextran sulphate sodium (DSS). Weight loss and colonoscopic score were increased significantly in Bim(-/-) mice compared to wild-type mice. As Bim is induced for the killing of autoreactive cells we determined the role of Bim in the regulation of lymphocyte survival at mucosal sites. Upon chronic dextran sulphate sodium (DSS)-induced colitis, Bim(-/-) animals exhibited an increased infiltrate of lymphocytes into the mucosa compared to wild-type mice. The number of autoreactive T cell receptor (TCR) Vβ8(+) lymphocytes was significantly higher in Bim(-/-) mice compared to wild-type controls. Impaired removal of autoreactive lymphocytes in Bim(-/-) mice upon chronic DSS-induced colitis may therefore contribute to aggravated mucosal inflammation.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital of Zürich, Zürich, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Leucht
authors.forename: M
authors.initials: M
authors.lastname: Caj
authors.forename: M
authors.initials: M
authors.lastname: Fried
authors.forename: G
authors.initials: G
authors.lastname: Rogler
authors.forename: M
authors.initials: M
authors.lastname: Hausmann
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency* / Q000235:genetics; D015551:Autoimmunity / Q000235:genetics; D000072224:Bcl-2-Like Protein 11; D016923:Cell Death / Q000235:genetics; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D016264:Dextran Sulfate / Q000009:adverse effects; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D012005:Rectal Prolapse / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D016207:Cytokines; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016264:Dextran Sulfate
keywords: Bim; Vβ8+ lymphocytes; apoptosis; autoreactive TCR