The Therapeutic Effects Of Treg Regulated By Lymphocyte Function-associated Antigen-1 On Inflammatory Bowel Disease

Background:It has been widely accepted that Treg cells exert an immunoprotective effect in inflammatory bowel disease(IBD).Lymphocyte Function-associatedAntigen-1(LFA-1)is involved in the differentiation and migration of Treg cells in IBD.Aims:To investigate the effect of LFA-1on IBD by regulating Treg cells and the regulating function of LFA-1 on Treg cells.Methods:Twenty wild type mice and twenty LFA-1 gene knockout(LFA-1-/-)countparts with same genetic background were randomly divided into colitis group(control group)and treatment group of IBD model,respectively.Colitis model was induced by drinking 2.5%DSS solution.General condition and histology of the colon were observed in each group.Mice from wild type and LFA-1-/-treatment group were injected Treg cells through the tail vein.Percentages of Treg cells in peripheral blood spleen and mesenteric lymph nodes were analyzed by flow cytometry.Serum levels of TGF-?1?IL-10?IL-17A and IFN-? were measured by ELISA and the mRNA level of TGF-?1 and IL-10 in colonic tissue was detected by real time PCR.Results:Compared to treatment group,wild type and LFA-1-/-colitis group had more significant weight loss.The colonic histological score of wild type treatment group was significantly lower than corresponding colitis groups,the colonic histological score of LFA-1-/-treatment group was no difference with corresponding colitis groups.Percentages of Treg cells of wild type treatment group in peripheral blood spleen and mesenteric lymph nodes were higher than the corresponding colitis group.Percentages of Treg cells of LFA-1-/-treatment group in peripheral blood and spleen had no significant difference with the corresponding colitis group,but percentages of Treg cells in mesenteric lymph nodes were higher than the corresponding colitis group.Serum levels of TGF-?1 and IL-10 of wild type and LFA-1-/-treatment group were higher than that of corresponding colitis group,and levels of IL-17A and IFN-?were lower than that of corresponding colitis group.Levels of TGF-?1 and IL-10 in wild type treatment group were increasing than that in LFA-1-/-treatment group.Expression of TGF-?1 mRNA in colonic tissue were increasing than that in corresponding colitis group.Expression of IL-10 mRNA in colonic tissue were decreasing than that in corresponding colitis group,and expression of TGF-?1mRNA and IL-10 mRNA in colonic tissue of wild type treatment group was also lower than that in LFA-1-/-treatment group.Conclusions:LFA-1 is involved in the functional regulation of Treg cells,including up-regulating Treg cells to secrete anti-inflammatory cytokines,such as TGF-?1 and IL-10.The therapeutic efficacy of Treg cells on LFA-1-/-mice model of IBD was lower than that in wild-type mice,which may be related to the inhabiting the function and cytokines secretion of Treg cells by LFA-1.