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Anti-mouse CD52 monoclonal antibody ameliorates intestinal epithelial barrier function in interleukin-10 knockout mice with spontaneous chronic colitis.
- Source :
-
Immunology . Feb2015, Vol. 144 Issue 2, p254-262. 9p. - Publication Year :
- 2015
-
Abstract
- Intestinal inflammation causes tight junction changes and death of epithelial cells, and plays an important role in the development of Crohn's disease (CD). CD52 monoclonal antibody (CD52 m Ab) directly targets the cell surface CD52 and is effective in depleting mature lymphocytes by cytolytic effects in vivo, leading to long-lasting changes in adaptive immunity. The aim of this study was to investigate the therapeutic effect of CD52 m Ab on epithelial barrier function in animal models of IBD. Interleukin-10 knockout mice (IL-10−/−) of 16 weeks with established colitis were treated with CD52 m Ab once a week for 2 weeks. Severity of colitis, CD4+ lymphocytes and cytokines in the lamina propria, epithelial expression of tight junction proteins, morphology of tight junctions, tumour necrosis factor- α (TNF- α)/TNF receptor 2 (TNFR2) m RNA expression, myosin light chain kinase (MLCK) expression and activity, as well as epithelial apoptosis in proximal colon were measured at the end of the experiment. CD52 m Ab treatment effectively attenuated colitis associated with decreased lamina propria CD4+ lymphocytes and interferon- γ/IL-17 responses in colonic mucosa in IL-10−/− mice. After CD52 m Ab treatment, attenuation of colonic permeability, increased epithelial expression and correct localization of tight junction proteins (occludin and zona occludens protein-1), as well as ameliorated tight junction morphology were observed in IL-10−/− mice. CD52 m Ab treatment also effectively suppressed the epithelial apoptosis, mucosa TNF- α m RNA expression, epithelial expression of long MLCK, TNFR2 and phosphorylation of MLC. Our results indicated that anti-CD52 therapy may inhibit TNF- α/TNFR2-mediated epithelial apoptosis and MLCK-dependent tight junction permeability by depleting activated T cells in the gut mucosa. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00192805
- Volume :
- 144
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 100255126
- Full Text :
- https://doi.org/10.1111/imm.12366