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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2014
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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. |
format | Online Article Text |
id | pubmed-4076595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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