Biajoux, Vincent Bignon, Alexandre Freitas, Christelle Martinez, Valérie Thelen, Marcus Lima, Guadalupe Jakez-Ocampo, Juan Emilie, Dominique Llorente, Luis Balabanian, Karl 2012-12-18 Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by B-cell hyperreactivity and the production of pathogenic anti-nuclear- directed auto-antibodies (Abs). B-cell ontogeny is partly dependent on the CXCL12/CXCR4 axis for which the contribution to SLE pathogenesis remains unclear. CXCR7, the novel receptor for CXCL12, is differentially expressed among memory B-cell subsets. However, its biological role in SLE remains to be explored. Methods: Relative CXCR4 and CXCR7 expression levels were compared by quantitative PCR in leukocytes from blood samples of 41 Mexican Mestizos patients with SLE and 45 ethnicity-matched healthy subjects. Intracellular and membrane expression of both receptors was analyzed by flow cytometry in naive and Ab-secreting B cells. B-cell responsiveness to CXCL12 was investigated using Transwell-based chemotaxis assays. Data were analyzed using the Kruskal-Wallis test for comparisons of values amongst healthy controls and patients with inactive or active SLE, and non-parametrically using the Mann–Whitney U-test for multiple comparisons and unpaired samples. Correlations were determined by Spearman’s ranking. Result: SLE leukocytes displayed reduced levels of CXCR4 and CXCR7 transcripts. In SLE patients, a significant defect in CXCR4 expression was detected at the surface of naive and Ab-secreting B cells, associated with an abnormal intracellular localization of the receptor. CXCR7 predominantly localized in cytosolic compartments of B cells from healthy and SLE individuals. Disease activity did not impact on these expression patterns. Altered receptor compartmentalization correlated with an impaired CXCL12-promoted migration of SLE B cells. Conclusions: Our data highlight a down- regulation of CXCL12 receptors on circulating B cells from SLE patients that likely influences their migratory behavior and distribution. application/pdf https://localhost:5000/ark:/12658/srd1319156 https://susi.usi.ch/global/documents/319156 https://susi.usi.ch/documents/319156/files/Biajoux_JTM_2012.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1186/1479-5876-10-251 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319156 info:eu-repo/semantics/openAccess CC BY Journal of translational medicine. - 2012, vol. 10, no. 1, p. 251-267 Autoimmunity Systemic Lupus erythematosus B cells Chemokines CXCR4 CXCR7 Migration info:eu-repo/classification/udc/61 Expression of CXCL12 receptors in B cells from Mexican Mestizos patients with systemic lupus erythematosus http://purl.org/coar/resource_type/c_6501