Effects Of Bete-catenin On The Differentiation Of TH17 In Animal Models Of Rheumatoid Arthritis

ObjectiveRheumatiod arthritis(RA)is a systemic autoimmune disease,which causes the chronic inflammatory disease in multiple organs.It has been reported that Th17 cells play important roles in the pathogenesis of disease.Recently,some studies have shown that Wnt/beta-catenin signal was involved in the pathogenic process of RA.However,the mechanism is still unclear.The purpose of this study is to investigate the effect of ?-catenin on the differentiation of th17 cell in animal model of RA.Methods8-10 weeks male C57BL/6 mice were divided into three groups : control group,CIA group,CIA +LICL group(?-catenin agonist).The mice were sacrificed in the peak phase of disease(day 55 after immunization),and the serum,ankle joint,knee joint,spleen,lymph nodes were collected.The serum was subjected to examine inflammatory cytokines(IL1?,IL23,IL6,IL17).Paraffin embedded sections(ankle joint,knee joint,spleen,lymph nodes)were used to HE,immunohistochemical stain and immunofluorescent stain.Western blot was performed to detect the expression of AKT and transcription factors(TCF1,TCF4,ROR?T,c-Jun)in spleen and lymph node).Results1 Compared the CIA group with the CIA+LICL group,the clinical score and onset of CIA+LICL group were significantly reduced.However,LICL could not affect the incidence of disease.2 HE staining showed that the inflammatory cell infiltration and the bone erosion were significantly increased in CIA group compared with control group,whereas LICL could significantly reduce the phenomena.3 The serum inflammatory cytokines(IL1?,IL23,IL6,IL17)were significantly upregulated in CIA group,while LICL treatment downregulated the levels.Meanwhile,IL17+ cells in ankle joint was also enhanced in CIA mice,however,LICL suppressed the infiltration of the cells.4 In spleen and lymph node,IL17+Th cells and CD68+macrophage were significantly increased in CIA group,whereas those in LICL group were reduced.5 The western blot results showed,expression of AKT,ROR?T,and c-Jun was significantly increased in spleen and lymph node of CIA mice,while LICL could be significantly reduced the levels.Interestingly,TCF1 was decreased in CIA spleen of CIA mice,and that in lymph node was increased.However,LICL treatment could reverse the expression of TCF1 both in spleen and lymph node.Moreover,TCF4 was increased only spleen of CIA+LICL group.ConclusionsThe findings suggest that ?-catenin decreased was closely related with the RA.In RA,?-catenin not only affect Th17 differentiation by inhibiting activity of macrophages,also directly affect it.In the spleen and lymph nodes of CIA,AKT/c-Jun can promote the differentiation of Th17.Furthermore,the mechanisms of ?-catenin/TCF1 how pathways affected Th17 differentiation in different immune organs of CIA.