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Journal articles
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.
Cited literature [64 references]
https://www.hal.inserm.fr/inserm-00788152
Contributor : Ed. Bmc Connect in order to contact the contributor
Submitted on : Wednesday, February 13, 2013 - 9:09:57 PM
Last modification on : Wednesday, October 14, 2020 - 3:47:23 AM
Long-term archiving on: : Tuesday, May 14, 2013 - 4:04:04 AM
Contributor : Ed. Bmc Connect in order to contact the contributor
Submitted on : Wednesday, February 13, 2013 - 9:09:57 PM
Last modification on : Wednesday, October 14, 2020 - 3:47:23 AM
Long-term archiving on: : Tuesday, May 14, 2013 - 4:04:04 AM