Effect Of Y-320 On Th17 Cells And Salivary Gland Function In ESS Mice

Objectives To explore the effect of IL-17 inhibitor Y-320 on Th17 and the function of salivary glands in experimental Sj(?)gren's syndrome(ESS)mice.Methods Eight-week-old C57BL/6 mice were selected and induced to establish animal models of ESS using complete Freund's adjuvant and homogenate of homologous mouse submandibular gland as an antigen.After successful modeling,subcutaneous injection of phsphate buffered PBS was used as the SS disease model group,Y-320 subcutaneous injection as the experimental group,and untreated C57BL/6 mice were injected subcutaneously with PBS as the normal control group.The changes in salivary flow rates at 0 weeks,8 weeks,and 12 weeks were observed in each group of mice after immunizations.At the 12 th week,the mice were sacrificed.The ratio of Th17 cells of spleen in each group was measured by flow cytometry.The submandibular glands were stained with HE to observe the lymphocytic infiltration of submandibular glands.IL-17,IL-6 and TGF-? of serum were detected by enzyme-linked immunosorbent assay.Results The salivary flow rate in the SS disease model group after immunizations showed a decreasing trend with the time.The salivary flow rate at 8th and 12 th week was significantly lower than that of the Y-320 experimental group and the normal control group(P<0.05).The salivary flow rate in the Y-320 experimental group at 8th and 12 th week was slightly lower than that in the normal control group,but it was not statistically difference.Flow cytometry results of mouse spleen cells showed that Th17 cells were significantly increased(P<0.05)in the SS model group compared with the normal control group.The proportion of Th17 in the Y-320 experimental group was significantly lower(P<0.05).There was not significantly different between the Y-320 experimental group and the normal group in the ratio of Th17 cells(P>0.05).Submandibular gland histopathological scores showed that the scores in the SS model group were significantly higher than those in the Y-320 experimental and the normal control group(P<0.05).The Y-320 experimental group had higher score than the normal control group(P<0.05).The levels of serum IL-17,IL-6 and TGF-? in the SS disease model group was higher than that in the control group(P<0.05),and the levels of these cytokines were not defferent in the Y-320 experimental group and the controll group.Conclusion The Y-320(IL-17 inhibitor)can improve the salivary flow rate in mice with the Sj(?)gren's syndrome,reduce the proportion of Th17 cells of spleen,and decrease the levels of serum IL-17,IL-6 and TGF-? to reduce the immune inflammatory response.At the same time,it can alleviate the infiltration degree of the lymphocytes in the submandib?lar gland tissue,improve the submandib?lar gland function.IL-17 inhibitors are expected to be used as new targets for SS therapy in clinical applications,but further research is needed.