To Explore The Role Of CXCL12-CXCR4/CXCR7 Pathway In The Immune Mechanism Of Primary Sjögren's Syndrome

Objectives:To explore the role of CXCL12-CXCR4/CXCR7 pathway in the pathogenesis of primary Sjogren’s syndrome(pSS).Methods:Peripheral blood samples were collected from pSS patients and healthy controls.The plasma CXCL12 level was determined by ELISA.The expression of CXCR4 and CXCR7 mRNA in peripheral blood mononuclear cells(PBMC)was measured by qPCR.Use flow cytometry to assess the expression of CXCR4 and CXCR7 in T cells and B cells and their subsets.Results:A total of 61 patients with pSS and 62 healthy controls were included.The plasma CXCL12 concentration in pSS patients was higher than that in healthy controls,but it was not statistically significant(277 pg/ml vs 228.3 pg/ml,P=0.33).There was no significant difference in CXCR4 and CXCR7 mRNA levels in PBMC between pSS patients and healthy controls,but the expression of CXCR7 tended to increase.The difference in the percentage of cell membrane CXCR4 positive in T cells between pSS patients and healthy controls was not significant(34%vs 26%,P=0.458),and not either in different T cell subsets.When relative total(i.e.both cell surface and intracellular)pools of CXCR4 was measured,the fraction of CXCR4 positive in T cells and different T cell subsets was comparable between pSS patients and healthy controls(81%vs 80%in T cells,P=0.817).CXCR7 seems to not appear on the surface of T cells and is located in the cytoplasm.When total pools of CXCR7 was assessed,there was no significant difference in the proportion of CXCR7 positive in T cells between pSS patients and healthy controls(51.4%vs 55.29%,P=0.513),and no difference was found in different T cell subpopulations.In terms of B cells,the proportion of naive B cells in B cells in pSS patients was significantly higher than that in healthy controls(65.34%vs 80.64%,P<0.001),while the percentage of unswitched memory B cells and switched memory B cells in B cells decreased.The percentage of cell membrane CXCR4 positive in B cells in pSS patients was higher than that in normal controls(84.54%vs 75.18%,P=0.003),but there was no difference in B cell subsets.The percentage of surface CXCR7 positive in B cells and its subsets between pSS and healthy controls was similar.When total CXCR4 was determined,there was no significant difference in the proportion of CXCR4 positive in B cells between the two groups(95.5%vs 94.8%,P=0.683),and no difference in the different subpopulations of B cells either.CXCR7 of B cells was mainly located in the cytoplasm.The difference in the percentage of CXCR7 positive in B cells between the two groups(47.79%vs 41.2%,P=0.513)was not significant,not in B cell subsets either.Conclusion:CXCR7 is mainly localized in the cytoplasm of B cells and T cells of pSS patients and healthy controls,while CXCR4 exists on the cell membrane and in the cytoplasm.The expression of CXCR4 on the surface of B cells in patients with pSS was higher than that in healthy controls,but no difference in total expression.There was no significant difference in the expression of CXCR7 in B cells between pSS patients and healthy controls.The expression of CXCR4 and CXCR7 between pSS patients and healthy controls in T cells was not significantly different.