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T cell specific Cxcr5 deficiency prevents rheumatoid arthritis.
Sci. Rep. 7:8933 (2017)
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.
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4.259
1.401
31
42
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Collagen-induced Arthritis; Primary Sjogrens-syndrome; B-cells; Dendritic Cells; Chemokine Receptors; Attracting Chemokine-1; Inflammatory Arthritis; Multiple-sclerosis; Lymphoid Follicles; Germinal-centers
Language
english
Publication Year
2017
HGF-reported in Year
2017
ISSN (print) / ISBN
2045-2322
e-ISSN
2045-2322
Journal
Scientific Reports
Quellenangaben
Volume: 7,
Issue: 1,
Article Number: 8933
Publisher
Nature Publishing Group
Publishing Place
London
Reviewing status
Peer reviewed
Institute(s)
CF Monoclonal Antibodies (CF-MAB)
POF-Topic(s)
30201 - Metabolic Health
Research field(s)
Helmholtz Diabetes Center
PSP Element(s)
G-502210-001
PubMed ID
28827539
WOS ID
WOS:000408107000067
Scopus ID
85027856019
Erfassungsdatum
2017-09-18