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

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.
Type de document :
Article dans une revue
Journal of Translational Medicine, BioMed Central, 2012, 10 (1), pp.251. 〈10.1186/1479-5876-10-251〉
Liste complète des métadonnées

Littérature citée [64 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00788152
Contributeur : Ed. Bmc <>
Soumis le : mercredi 13 février 2013 - 21:09:57
Dernière modification le : vendredi 17 février 2017 - 14:30:24
Document(s) archivé(s) le : mardi 14 mai 2013 - 04:04:04

Identifiants

Collections

Citation

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〉

Partager

Métriques

Consultations de la notice

366

Téléchargements de fichiers

352