The Effect Of Lymphocyte Function Associated Antigen-1on Inflammatory Bowel Disease By Regulating Treg Cells

Background: Treg cells are lymphocyte subsets and play the immunosuppressiveeffect in inflammatory bowel disease (IBD). Lymphocyte function-associatedantigen-1(LFA-1) is involved in T cell differentiation and function.Aims: The present study is to investigate the effects and mechanism of LFA-1on theregulatign Treg cell differentiation in the pathogenesis of IBD.Methods: LFA-1gene knocked-out mice and the same genetic background of wildmouse were divided into four groups which named as LFA-1-/-control,LFA-1-/-colitis, control, and colitis, respectively. IBD model was induced by4.5%DSS. The percentage of CD4+and Treg cells in peripheral blood were detected byflow cytometry. Serum cytokines were measured by ELISA. The expression ofFoxp3mRNA was detected by Real-time polymerase chain reaction.Results: The body weight dropped in colitis groups compared with the controlgroups respectively（P=0.000）,the same result was found in colon length. The moreseverity of colitis was observed in LFA-1deficient mice. There is no significantdifference between two colitis groups in colon length and the histological scores.The declined weight of LFA-1deficient mice was high than common mice betweentwo colitis group（sP=0.001）. The percentage of CD4+(LFA-1-/-control vs control：4.38±1.09%vs14.40±1.16%，P=0.000；LFA-1-/-colitis vs colitis：1.65±0.11%vs15.09±1.23%，P=0.000；) and Treg (LFA-1-/-control vs control：1.89±0.12%vs5.22±0.36%, P=0.000； LFA-1-/-colitis vs colitis：1.77±0.34%vs2.54±0.37%, P=0.803；)cell in LFA-1deficient mice were significantly decreased compared withcommon mice. The proportion of LFA-1in Treg cell surface of colitis declinedcompared with control group(54.86±4.03%vs67.77±2.11%，P=0.014). The serumlevel TGF-β1in colitis、 control、 LFA-1-/-colitis and LFA-1-/-control was69.90±3.90ng/ml、22.30±0.90ng/ml、65.50±4.30ng/ml and21.10±0.70ng/ml，inwhich both colitis were higher than their control groups respectively. LFA-1-/-colitiswere higher than LFA-1-/-control but lower than colitis group (LFA-1-/-colitis vsLFA-1-/-control, LFA-1-/-colitis vs colitis, P=0.000). The same results were foundin the level of IL10、IL17A.The expression of Foxp3mRNA were increased incolitis compared with control (2.80±0.76vs1.49±0.42， P=0.172) andLFA-1-/-colitis compared with LFA-1-/-control (3.69±0.77vs1.18±0.42，P=0.02),respectively.Conclusion: LFA-1was involved in the pathogensis of IBD and mechanism mightbe related to effects of LFA-1on regulating Treg cells differentiation and cytokinessecretion.