摘要 : Genetic investigations of Sjogren's syndrome (SS) have identified a susceptibility locus at p23.3 of chromosome 11, which contains the CXCR5 gene. C-X-C motif chemokine receptor 5 (CXCR5) is a chemokine receptor expressed on B and... 展开 Genetic investigations of Sjogren's syndrome (SS) have identified a susceptibility locus at p23.3 of chromosome 11, which contains the CXCR5 gene. C-X-C motif chemokine receptor 5 (CXCR5) is a chemokine receptor expressed on B and T cell subsets, and binds the chemotactic ligand C-X-C motif chemokine ligand 13 (CXCL13). In this study we aimed to link the genetic association with functional effects and explore the CXCR5/CXCL13 axis in SS. Expression quantitative trait loci analysis of the 11q23.3 locus was performed using B cell mRNA expression data from genotyped individuals. Lymphocyte surface markers were assessed by flow cytometry, and CXCL13 levels by a proximity extension assay. CXCR5(+) and CXCL13(+) cells in minor salivary glands were detected using immunohistochemistry. Our results demonstrated that SS-associated genetic polymorphisms affected the expression of CXCR5 (P<0<bold></bold>01). Notably, a decreased percentage of CXCR5(+) cells, with lower CXCR5 expression, was observed for most circulating B and T cell subsets in SS patients, reaching statistical significance in CD19(+)CD27(+)immunoglobulin (Ig)D+ marginal zone (P<0<bold></bold>001), CD19(+)CD27(+)IgD(-) memory (P<0<bold></bold>05) and CD27-IgD double-negative (P<0<bold></bold>01) B cells and CD4(+)CXCR3(-)CCR6(+) Th17 cells (P<0<bold></bold>05). CXCL13 levels were increased in patient plasma (P<0<bold></bold>001), and immunohistochemical staining revealed expression of CXCL13 and higher numbers of CXCR5(+) cells (P<0<bold></bold>0001) within focal infiltrates and interstitially in salivary glands of SS patients. In conclusion, we link a genetic susceptibility allele for SS to a functional phenotype in terms of decreased CXCR5 expression. The decrease of CXCR5(+) cells in circulation was also related to homing of B and T cells to the autoimmune target organ. Therapeutic drugs targeting the CXCR5/CXCL13 axis may be useful in SS. 收起