2018/02/17 by Lara A. Aqrawi, L A Aqrawi, M Ivanchenko +21 · 1 citation
Chemistry · Medicine · #Antibody #B cell #Biology #C-C chemokine receptor type 6 #CD19 #CXCL13 #CXCR3 #CXCR5 #Chemistry #Chemokine #Chemokine receptor #Chemokine receptors and signaling #Endocrinology #Flow cytometry #Immune system #Immunoglobulin D #Immunology #Internal medicine #Medicine #Molecular biology #Salivary Gland Disorders and Functions #Salivary Gland Tumors Diagnosis and Treatment #XCL2
paper · doi:10.1111/cei.13118
openalex publication_date 2018/02/17 · crossref created 2018/02/17 · crossref issued 2018/03/24 · crossref published 2018/03/24 · crossref published-online 2018/03/24 · crossref published-print 2018/05/25 · crossref deposited 2022/01/01 · openalex created_date 2025/10/10 · crossref indexed 2026/07/29 · openalex updated_date 2026/07/29
Summary Genetic investigations of Sjögren'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 < 0·01). 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 < 0·001), CD19+CD27+IgD– memory (P < 0·05) and CD27-IgD double-negative (P < 0·01) B cells and CD4+CXCR3–CCR6+ Th17 cells (P < 0·05). CXCL13 levels were increased in patient plasma (P < 0·001), and immunohistochemical staining revealed expression of CXCL13 and higher numbers of CXCR5+ cells (P < 0·0001) 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.