A myostatin-CCL20–CCR6 axis regulates Th17 cell recruitment to inflamed joints in experimental arthritis

Abstract The interactions of fibroblast-like synoviocyte (FLS)-derived pro-inflammatory cytokines/chemokines and immune cells support the recruitment and activation of inflammatory cells in RA. Here, we show for the first time that the classical myokine myostatin (GDF-8) is involved in the recruitme...

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Autores principales:	Michelle Fennen, Toni Weinhage, Vanessa Kracke, Johanna Intemann, Georg Varga, Corinna Wehmeyer, Dirk Foell, Adelheid Korb-Pap, Thomas Pap, Berno Dankbar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0e68a05c59a446c9abd58a77cfaf8633
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spelling	oai:doaj.org-article:0e68a05c59a446c9abd58a77cfaf86332021-12-02T16:15:06ZA myostatin-CCL20–CCR6 axis regulates Th17 cell recruitment to inflamed joints in experimental arthritis10.1038/s41598-021-93599-62045-2322https://doaj.org/article/0e68a05c59a446c9abd58a77cfaf86332021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93599-6https://doaj.org/toc/2045-2322Abstract The interactions of fibroblast-like synoviocyte (FLS)-derived pro-inflammatory cytokines/chemokines and immune cells support the recruitment and activation of inflammatory cells in RA. Here, we show for the first time that the classical myokine myostatin (GDF-8) is involved in the recruitment of Th17 cells to inflammatory sites thereby regulating joint inflammation in a mouse model of TNFalpha-mediated chronic arthritis. Mechanistically, myostatin-deficiency leads to decreased levels of the chemokine CCL20 which is associated with less infiltration of Th17 cells into the inflamed joints. In vitro, myostatin alone or in combination with IL-17A enhances the secretion of CCL20 by FLS whereas myostatin-deficiency reduces CCL20 secretion, associated with an altered transmigration of Th17 cells. Thus, the communication between activated FLS and Th17 cells through myostatin and IL-17A may likely contribute to a vicious cycle of inflammation, accounting for the persistence of joint inflammation in chronic arthritis. Blockade of the CCL20–CCR6 axis by inhibition of myostatin may, therefore, be a promising treatment option for chronic inflammatory diseases such as arthritis.Michelle FennenToni WeinhageVanessa KrackeJohanna IntemannGeorg VargaCorinna WehmeyerDirk FoellAdelheid Korb-PapThomas PapBerno DankbarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michelle Fennen Toni Weinhage Vanessa Kracke Johanna Intemann Georg Varga Corinna Wehmeyer Dirk Foell Adelheid Korb-Pap Thomas Pap Berno Dankbar A myostatin-CCL20–CCR6 axis regulates Th17 cell recruitment to inflamed joints in experimental arthritis
description	Abstract The interactions of fibroblast-like synoviocyte (FLS)-derived pro-inflammatory cytokines/chemokines and immune cells support the recruitment and activation of inflammatory cells in RA. Here, we show for the first time that the classical myokine myostatin (GDF-8) is involved in the recruitment of Th17 cells to inflammatory sites thereby regulating joint inflammation in a mouse model of TNFalpha-mediated chronic arthritis. Mechanistically, myostatin-deficiency leads to decreased levels of the chemokine CCL20 which is associated with less infiltration of Th17 cells into the inflamed joints. In vitro, myostatin alone or in combination with IL-17A enhances the secretion of CCL20 by FLS whereas myostatin-deficiency reduces CCL20 secretion, associated with an altered transmigration of Th17 cells. Thus, the communication between activated FLS and Th17 cells through myostatin and IL-17A may likely contribute to a vicious cycle of inflammation, accounting for the persistence of joint inflammation in chronic arthritis. Blockade of the CCL20–CCR6 axis by inhibition of myostatin may, therefore, be a promising treatment option for chronic inflammatory diseases such as arthritis.
format	article
author	Michelle Fennen Toni Weinhage Vanessa Kracke Johanna Intemann Georg Varga Corinna Wehmeyer Dirk Foell Adelheid Korb-Pap Thomas Pap Berno Dankbar
author_facet	Michelle Fennen Toni Weinhage Vanessa Kracke Johanna Intemann Georg Varga Corinna Wehmeyer Dirk Foell Adelheid Korb-Pap Thomas Pap Berno Dankbar
author_sort	Michelle Fennen
title	A myostatin-CCL20–CCR6 axis regulates Th17 cell recruitment to inflamed joints in experimental arthritis
title_short	A myostatin-CCL20–CCR6 axis regulates Th17 cell recruitment to inflamed joints in experimental arthritis
title_full	A myostatin-CCL20–CCR6 axis regulates Th17 cell recruitment to inflamed joints in experimental arthritis
title_fullStr	A myostatin-CCL20–CCR6 axis regulates Th17 cell recruitment to inflamed joints in experimental arthritis
title_full_unstemmed	A myostatin-CCL20–CCR6 axis regulates Th17 cell recruitment to inflamed joints in experimental arthritis
title_sort	myostatin-ccl20–ccr6 axis regulates th17 cell recruitment to inflamed joints in experimental arthritis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0e68a05c59a446c9abd58a77cfaf8633
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A myostatin-CCL20–CCR6 axis regulates Th17 cell recruitment to inflamed joints in experimental arthritis

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