T cell specific Cxcr5 deficiency prevents rheumatoid arthritis

Abstract 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 impac...

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Autores principales:	Georgios L. Moschovakis, Anja Bubke, Michaela Friedrichsen, Christine S. Falk, Regina Feederle, Reinhold Förster
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/26ad5b1349cb4222bb959cc284c84ee8
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spelling	oai:doaj.org-article:26ad5b1349cb4222bb959cc284c84ee82021-12-02T16:06:43ZT cell specific Cxcr5 deficiency prevents rheumatoid arthritis10.1038/s41598-017-08935-62045-2322https://doaj.org/article/26ad5b1349cb4222bb959cc284c84ee82017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08935-6https://doaj.org/toc/2045-2322Abstract 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.Georgios L. MoschovakisAnja BubkeMichaela FriedrichsenChristine S. FalkRegina FeederleReinhold FörsterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Georgios L. Moschovakis Anja Bubke Michaela Friedrichsen Christine S. Falk Regina Feederle Reinhold Förster T cell specific Cxcr5 deficiency prevents rheumatoid arthritis
description	Abstract 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.
format	article
author	Georgios L. Moschovakis Anja Bubke Michaela Friedrichsen Christine S. Falk Regina Feederle Reinhold Förster
author_facet	Georgios L. Moschovakis Anja Bubke Michaela Friedrichsen Christine S. Falk Regina Feederle Reinhold Förster
author_sort	Georgios L. Moschovakis
title	T cell specific Cxcr5 deficiency prevents rheumatoid arthritis
title_short	T cell specific Cxcr5 deficiency prevents rheumatoid arthritis
title_full	T cell specific Cxcr5 deficiency prevents rheumatoid arthritis
title_fullStr	T cell specific Cxcr5 deficiency prevents rheumatoid arthritis
title_full_unstemmed	T cell specific Cxcr5 deficiency prevents rheumatoid arthritis
title_sort	t cell specific cxcr5 deficiency prevents rheumatoid arthritis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/26ad5b1349cb4222bb959cc284c84ee8
work_keys_str_mv	AT georgioslmoschovakis tcellspecificcxcr5deficiencypreventsrheumatoidarthritis AT anjabubke tcellspecificcxcr5deficiencypreventsrheumatoidarthritis AT michaelafriedrichsen tcellspecificcxcr5deficiencypreventsrheumatoidarthritis AT christinesfalk tcellspecificcxcr5deficiencypreventsrheumatoidarthritis AT reginafeederle tcellspecificcxcr5deficiencypreventsrheumatoidarthritis AT reinholdforster tcellspecificcxcr5deficiencypreventsrheumatoidarthritis
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T cell specific Cxcr5 deficiency prevents rheumatoid arthritis

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