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Expression of CXCL12 receptors in B cells from Mexican Mestizos patients with systemic lupus erythematosus

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2012
Author Biajoux Vincent, Biajoux Vincent, Bignon Alexandre, Bignon Alexandre, Freitas Christelle, Freitas Christelle, Martinez Valérie, Martinez Valérie, Martinez Valérie, Thelen Marcus, Lima Guadalupe, Jakez-Ocampo Juan, Emilie Dominique, Emilie Dominique, Emilie Dominique, Llorente Luis, Balabanian Karl, Balabanian Karl,
Project Conventional and atypical chemokine receptors: different mechanisms of function and common responses
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Original article (peer-reviewed)

Journal Journal of Translational Medicine
Volume (Issue) 10(1)
Page(s) 251
Title of proceedings Journal of Translational Medicine
DOI 10.1186/1479-5876-10-251

Open Access

Abstract

Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by B-cell hyper-reactivity 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. © 2012 Biajoux et al.; licensee BioMed Central Ltd.
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