Anti‐mouse CD52 monoclonal antibody ameliorates intestinal epithelial barrier function in interleukin‐10 knockout mice with spontaneous chronic colitis

• DOI: 10.1111/imm.12366
• Publication Date: 2014-08-01T21:59:41Z
• Authors: Honggang Wang; Jianning Dong; Peiliang Shi; Jianhui Liu; Lugen Zuo; Yi Li; Jianfeng Gong; Lili Gu; Jie Zhao; Liang Zhang; Wei Zhang; Weiming Zhu; Ning Li; Jieshou Li
• Keywords: CD52; Lamina propria; Barrier function; Knockout mouse; Intestinal mucosa

Intestinal inflammation causes tight junction changes and death of epithelial cells, plays an important role in the development Crohn's disease (CD). CD52 monoclonal antibody (CD52 mAb) directly targets cell surface is effective depleting mature lymphocytes by cytolytic effects vivo, leading to long-lasting adaptive immunity. The aim this study was investigate therapeutic effect mAb on barrier function animal models IBD. Interleukin-10 knockout mice (IL-10(-/-) ) 16 weeks with established colitis were treated once a week for 2 weeks. Severity colitis, CD4(+) cytokines lamina propria, expression proteins, morphology junctions, tumour necrosis factor-α (TNF-α)/TNF receptor (TNFR2) mRNA expression, myosin light chain kinase (MLCK) activity, as well apoptosis proximal colon measured at end experiment. treatment effectively attenuated associated decreased propria interferon-γ/IL-17 responses colonic mucosa IL-10(-/-) mice. After treatment, attenuation permeability, increased correct localization proteins (occludin zona occludens protein-1), ameliorated observed also suppressed apoptosis, TNF-α long MLCK, TNFR2 phosphorylation MLC. Our results indicated that anti-CD52 therapy may inhibit TNF-α/TNFR2-mediated MLCK-dependent permeability activated T cells gut mucosa.