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Cardiac fibroblasts mediate IL-17A–driven inflammatory dilated cardiomyopathy

Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in individuals below the age of 40. We recently reported that IL-17A is required for the development of DCMi. We show a novel pathway connecting IL-17A, cardiac fibroblasts (CFs), GM-CSF, and heart-infiltrating myeloid cell...

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Autores principales: Wu, Lei, Ong, SuFey, Talor, Monica V., Barin, Jobert G., Baldeviano, G. Christian, Kass, David A., Bedja, Djahida, Zhang, Hao, Sheikh, Asfandyar, Margolick, Joseph B., Iwakura, Yoichiro, Rose, Noel R., Čiháková, Daniela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076595/
https://www.ncbi.nlm.nih.gov/pubmed/24935258
http://dx.doi.org/10.1084/jem.20132126
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author Wu, Lei
Ong, SuFey
Talor, Monica V.
Barin, Jobert G.
Baldeviano, G. Christian
Kass, David A.
Bedja, Djahida
Zhang, Hao
Sheikh, Asfandyar
Margolick, Joseph B.
Iwakura, Yoichiro
Rose, Noel R.
Čiháková, Daniela
author_facet Wu, Lei
Ong, SuFey
Talor, Monica V.
Barin, Jobert G.
Baldeviano, G. Christian
Kass, David A.
Bedja, Djahida
Zhang, Hao
Sheikh, Asfandyar
Margolick, Joseph B.
Iwakura, Yoichiro
Rose, Noel R.
Čiháková, Daniela
author_sort Wu, Lei
collection PubMed
description Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in individuals below the age of 40. We recently reported that IL-17A is required for the development of DCMi. We show a novel pathway connecting IL-17A, cardiac fibroblasts (CFs), GM-CSF, and heart-infiltrating myeloid cells with the pathogenesis of DCMi. Il17ra(−/−) mice were protected from DCMi, and this was associated with significantly diminished neutrophil and Ly6Chi monocyte/macrophage (MO/MΦ) cardiac infiltrates. Depletion of Ly6Chi MO/MΦ also protected mice from DCMi. Mechanistically, IL-17A stimulated CFs to produce key chemokines and cytokines that are critical downstream effectors in the recruitment and differentiation of myeloid cells. Moreover, IL-17A directs Ly6Chi MO/MΦ in trans toward a more proinflammatory phenotype via CF-derived GM-CSF. Collectively, this IL-17A–fibroblast–GM-CSF–MO/MΦ axis could provide a novel target for the treatment of DCMi and related inflammatory cardiac diseases.
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spelling pubmed-40765952014-12-30 Cardiac fibroblasts mediate IL-17A–driven inflammatory dilated cardiomyopathy Wu, Lei Ong, SuFey Talor, Monica V. Barin, Jobert G. Baldeviano, G. Christian Kass, David A. Bedja, Djahida Zhang, Hao Sheikh, Asfandyar Margolick, Joseph B. Iwakura, Yoichiro Rose, Noel R. Čiháková, Daniela J Exp Med Article Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in individuals below the age of 40. We recently reported that IL-17A is required for the development of DCMi. We show a novel pathway connecting IL-17A, cardiac fibroblasts (CFs), GM-CSF, and heart-infiltrating myeloid cells with the pathogenesis of DCMi. Il17ra(−/−) mice were protected from DCMi, and this was associated with significantly diminished neutrophil and Ly6Chi monocyte/macrophage (MO/MΦ) cardiac infiltrates. Depletion of Ly6Chi MO/MΦ also protected mice from DCMi. Mechanistically, IL-17A stimulated CFs to produce key chemokines and cytokines that are critical downstream effectors in the recruitment and differentiation of myeloid cells. Moreover, IL-17A directs Ly6Chi MO/MΦ in trans toward a more proinflammatory phenotype via CF-derived GM-CSF. Collectively, this IL-17A–fibroblast–GM-CSF–MO/MΦ axis could provide a novel target for the treatment of DCMi and related inflammatory cardiac diseases. The Rockefeller University Press 2014-06-30 /pmc/articles/PMC4076595/ /pubmed/24935258 http://dx.doi.org/10.1084/jem.20132126 Text en © 2014 Wu et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Wu, Lei
Ong, SuFey
Talor, Monica V.
Barin, Jobert G.
Baldeviano, G. Christian
Kass, David A.
Bedja, Djahida
Zhang, Hao
Sheikh, Asfandyar
Margolick, Joseph B.
Iwakura, Yoichiro
Rose, Noel R.
Čiháková, Daniela
Cardiac fibroblasts mediate IL-17A–driven inflammatory dilated cardiomyopathy
title Cardiac fibroblasts mediate IL-17A–driven inflammatory dilated cardiomyopathy
title_full Cardiac fibroblasts mediate IL-17A–driven inflammatory dilated cardiomyopathy
title_fullStr Cardiac fibroblasts mediate IL-17A–driven inflammatory dilated cardiomyopathy
title_full_unstemmed Cardiac fibroblasts mediate IL-17A–driven inflammatory dilated cardiomyopathy
title_short Cardiac fibroblasts mediate IL-17A–driven inflammatory dilated cardiomyopathy
title_sort cardiac fibroblasts mediate il-17a–driven inflammatory dilated cardiomyopathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076595/
https://www.ncbi.nlm.nih.gov/pubmed/24935258
http://dx.doi.org/10.1084/jem.20132126
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