T cell specific Cxcr5 deficiency prevents rheumatoid arthritis

• Published in: Scientific reports Vol. 7; no. 1; pp. 8933 - 13
• Main Authors: Moschovakis, Georgios L., Bubke, Anja, Friedrichsen, Michaela, Falk, Christine S., Feederle, Regina, Förster, Reinhold
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.08.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/21; 13/31; 14/1; 14/63; 631/250/38; 631/250/98; 64/110; 692/4023/1670/498; Antibody response; Autoimmune diseases; Cell adhesion & migration; Collagen; Collagen (type II); CXCL13 protein; CXCR5 protein; Follicles; Humanities and Social Sciences; Immunoglobulin G; Inflammation; Leukocyte migration; Localization; Lymphocyte receptors; Lymphocytes B; Lymphocytes T; multidisciplinary; Rheumatoid arthritis; Science; Science (multidisciplinary); T cell receptors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-08935-6

The chemokine receptor CXCR5 is primarily expressed on B cells and Tfh cells and facilitates their migration towards B cell follicles. In the present study we investigated the role of the CXCL13/CXCR5 axis in the pathogenesis of rheumatoid arthritis (RA) and specifically addressed the impact of CXCR5-mediated T and B cell migration in this disease. Employing collagen-induced arthritis (CIA) we identify CXCR5 as an absolutely essential factor for the induction of inflammatory autoimmune arthritis. Cxcr5 -deficient mice and mice selectively lacking Cxcr5 on T cells were completely resistant to CIA, showed impaired germinal center responses and failed to mount an IgG1 antibody response to collagen II. Selective ablation of CXCR5 expression in B cells also led to suppression of CIA owing to diminished GC responses in secondary lymphoid organs (SLO) and impaired anti-collagen II antibody production. Chimeric mice harboring Cxcr5 -proficient and Cxcr5 -deficient immune cells revealed SLO and not the synovial tissue as the compartment where CXCR5-mediated cell migration induces autoimmune inflammation in arthritis. Thus our data demonstrate that CXCR5-mediated co-localization of Tfh cells and B cells in SLOs is absolutely essential for the induction of RA and identify CXCR5 and Tfh cells as promising therapeutic targets for the treatment of RA.