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

Journal of Translational Medicine

Research

Juan Jakez-Ocampo¹  Luis Llorente¹  Guadalupe Lima¹  Marcus Thelen²  Vincent Biajoux³  Christelle Freitas³  Karl Balabanian³  Alexandre Bignon³  Dominique Emilie⁴  Valérie Martinez⁵ 

[1] Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Mèdicas y Nutriciòn Salvador Zubiràn, Mexico City, Mexico;Institute for Research in Biomedicine, Bellinzona, Switzerland;Université Paris-Sud, Laboratoire "Cytokines, Chimiokines et Immunopathologie", UMR_S996, Clamart, France;INSERM, Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), Clamart, France;Université Paris-Sud, Laboratoire "Cytokines, Chimiokines et Immunopathologie", UMR_S996, Clamart, France;INSERM, Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), Clamart, France;Service de Microbiologie-Immunologie Biologique, AP-HP, Hôpital Antoine-Béclère, Clamart, France;Université Paris-Sud, Laboratoire "Cytokines, Chimiokines et Immunopathologie", UMR_S996, Clamart, France;INSERM, Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), Clamart, France;Service de Médecine Interne et d’Immunologie Clinique, AP-HP, Hôpital Antoine-Béclère, Clamart, France;

关键词: Autoimmunity;    Systemic Lupus Erythematosus;    B cells;    Chemokines;    CXCR4;    CXCR7;    Migration;   

DOI  :  10.1186/1479-5876-10-251

 received in 2012-09-18, accepted in 2012-12-14,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundSystemic 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.MethodsRelative 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.ResultSLE 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.ConclusionsOur data highlight a down-regulation of CXCL12 receptors on circulating B cells from SLE patients that likely influences their migratory behavior and distribution.

【 授权许可】

Unknown   
© Biajoux et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.