Effect Of Lymphocyte Function-associated Antigen-1 On Plasticity Of Th17 Cells In Inflammatory Bowel Disease

Background:Thl7 cells play a crucial role in the pathogenesis of inflammatory bowel disease.Emerging data suggests that Thl7 cells display substantial developmental plasticity.LFA-1 participates in the activation and recruitment of lymphocyte.Aims:To investigate the influence of LFA-1 on the plasticity of Thl7 cells.Methods:LFA-1 deficient mice and wild type mice under same genetic background were randomly divided into four groups:wild-type control group.wild-type treated group.LFA-1-l-control group.LFA-1--1 treated group.Colitis was induced by drinking 2.5%DSS solution in all groups.Naive T cells were separated by magnetic-activated cell sorting(MACS)and induced under Thl7 conditions in vitro.Highly enriched Th17 cells were transferred into wild-type and LFA-1-1-treated groups on the fourth day.General condition and histology were observed in all groups.Cells in spleen、mesenteric lymph nodes(MLN)and the colon lamina propria(CLP)were analyzed by flow cytometry.Expression of Th17 and Thl associated transcription factors and cytokines mRNA were analyzed by real time PCR,and serum levels of IL17 and IFN-γ were detected by ELISA method.Results:Transferring Thl7 cells can enhance the inflammation and the ratios of Thl 7 and Th1 cells in spleen,MLN and CLP increased in wild type and LFA-1-1-treated groups.Percentages of Tcl and Tc17 cells in LFA-1-1-mice had significant increase compared with wild-type mice.Expressions of IL-17,IFN-γ and ROR-γ t mRNA increased in wild type treated group but decreased in LFA-1-1-treated group.Serum levels of IL-17 and aFN-γ increased in both wild-type and LFA-1-1-treated groups.Conclusions:Thl7 cells can transfer to Thl-like cells in inflammatory bowel disease.Deficiency of LFA-1 gene can influence the effect and promote the polarizations of Tc17/Tcl.