Effect Of Klotho On Th17 Cell Differentiation In A Mouse Experimental Autoimmune Encephalomyelitis Model

ObjectiveThe aim of this study is to investigate the effect of Klotho on Th17 cell differentiation in MS using the experimental autoimmune encephalomyelitis(EAE)model.MethodsFemale C57BL/6 mice aged 8-10 weeks were divided into three groups: the EAE,the EAE+KL,EAE+KL(L),EAE+KL(H).The polutation of Th1,Th17,and Treg in spleen was detected by FACS.The secretion cytokines(IL-6,IL-23,IL-10,IL-4.)in culture media was detected by ELISA.Western blot was used to detect the changes of PI3 K,NF-?B and ROR?T in spleen.immunofluorescence staining was used to observe the distribution of Klotho,IL-17 and CD68.ResultsCompared the EAE group with the EAE+KL groups,the onset time and clinical maximum score of EAE+KL groups were significantly lower than in the EAE group,however,there is no difference in the rate of incidence.FACS showed that the population of Th1 and Th17 was significantly suppressed,while Treg was slightly increased with KL treatment.The levels of IL-23,IL-6,IL-17,and IFN-? were significantly decreased in the EAE+KL group,while IL-10 and IL-4 leves significantly higher in the EAE+KL group.Western blot showed PI3 K,NF-?B and ROR?T in EAE+KL group were decreased compared with EAE group.The double immunofluorescence of mouse spleen IL-17 positive cells and CD68 positive cells were significantly reduced in EAE+KL group,however,only CD68 and Klotho double-stained cells were significantly increased in mice spleen.ConclusionsIn the spleen,KL inhibits Th17 cell differentiation by inhibiting the NF-?B signal transduction pathway,and KL can also inhibit the expression of macrophages and thus inhibit the auxiliary role of Th0 to Th17 cell differentiation.This conclusion can provide theoretical basis for the research of multiple sclerosis.