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Moschovakis, G.L.* ; Bubke, A.* ; Friedrichsen, M.* ; Falk, C.S.* ; Feederle, R. ; Förster, R.*

T cell specific Cxcr5 deficiency prevents rheumatoid arthritis.

Sci. Rep. 7:8933 (2017)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
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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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Collagen-induced Arthritis; Primary Sjogrens-syndrome; B-cells; Dendritic Cells; Chemokine Receptors; Attracting Chemokine-1; Inflammatory Arthritis; Multiple-sclerosis; Lymphoid Follicles; Germinal-centers
Sprache englisch
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 7, Heft: 1, Seiten: , Artikelnummer: 8933 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) CF Monoclonal Antibodies (CF-MAB)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502210-001
PubMed ID 28827539
DOI 10.1038/s41598-017-08935-6
WOS ID WOS:000408107000067
Scopus ID 85027856019
Erfassungsdatum 2017-09-18
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