CD4 T cells are required for both development and maintenance of disease in a new mouse model of reversible colitis

• DOI: 10.1038/mi.2015.93
• Publication Date: 2015-09-16T12:49:57Z
• Authors: J Brasseit; E Althaus-Steiner; M Faderl; N Dickgreber; L Saurer; V Genitsch; T Dolowschiak; H Li; D Finke; W-D Hardt; K D McCoy; A J Macpherson; N Corazza; M Noti; C Mueller
• Keywords: CD4-Positive T-Lymphocytes; Mice, Knockout; 0301 basic medicine; Wound Healing; Tumor Necrosis Factor-alpha; Colitis; Inflammatory Bowel Diseases; Adoptive Transfer; Lymphocyte Depletion; Helicobacter Infections; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; Gene Expression Regulation; Cell Movement; Animals; Humans; Intestinal Mucosa; Cells, Cultured

Current therapies to treat inflammatory bowel diseases have limited efficacy, significant side effects, and often wane over time. Little is known about the cellular molecular mechanisms operative in process of mucosal healing from colitis. To study such events, we developed a new model reversible colitis which adoptive transfer CD4+CD45RBhi T cells into Helicobacter typhlonius–colonized lymphopenic mice resulted rapid onset colonic inflammation that was through depletion colitogenic cells. Remission associated with an improved clinical histopathological score, reduced immune cell infiltration intestinal mucosa, altered gene expression profiles, regeneration mucus layer, restoration epithelial barrier integrity. Notably, were not only critical for induction but also maintenance disease. Depletion drop tumor necrosis factor α (TNFα) levels sites inflammation. Although neutralization TNFα prevented colitis, anti-TNFα treatment established disease failed resolve Collectively, this provides important research tool dynamics chronic remitting–relapsing disorders.