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

Vincent Biajoux 1, 2 Alexandre Bignon 1, 2 Christelle Freitas 1, 2 Valérie Martinez 1, 2, 3 Marcus Thelen 4 Guadalupe Lima 5 Juan Jakez-Ocampo 5 Dominique Emilie 1, 2, 6 Luis Llorente 5 Karl Balabanian 1, 2, *
* Auteur correspondant
1 LabEX LERMIT - Laboratoire de Recherche sur le Médicament et l'Innovation Thérapeutique
2 Cytokines, chimiokines et immunopathologie
3 Service de Médecine Interne et d'Immunologie Clinique
4 Signal-Transduction Research Department
5 Department of Immunology and Rheumatology
6 Service de Microbiologie-Immunologie Biologique
Abstract : 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.
Keywords : Autoimmunity Systemic Lupus Erythematosus B cells Chemokines CXCR4 CXCR7 Migration
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Journal of Translational Medicine, BioMed Central, 2012, 10 (1), pp.251. 〈10.1186/1479-5876-10-251〉
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Vincent Biajoux, Alexandre Bignon, Christelle Freitas, Valérie Martinez, Marcus Thelen, et al.. Expression of CXCL12 receptors in B cells from Mexican Mestizos patients with systemic lupus erythematosus.. Journal of Translational Medicine, BioMed Central, 2012, 10 (1), pp.251. 〈10.1186/1479-5876-10-251〉. 〈inserm-00788152〉

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