Sca-1+ cardiac fibroblasts promote development of heart failure

Guobao Chen, William Bracamonte-Baran, Nicola L. Diny, Xuezhou Hou, Monica V. Talor, Kai Fu, Yue Liu, Giovanni Davogustto, Hernan Vasquez, Heinrich Taegtmeyer, O. Howard Frazier, Ari Waisman, Simon Conway, Fengyi Wan, Daniela Čiháková

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The causative effect of GM-CSF produced by cardiac fibroblasts to development of heart failure has not been shown. We identified the pathological GM-CSF-producing cardiac fibroblast subset and the specific deletion of IL-17A signaling to these cells attenuated cardiac inflammation and heart failure. We describe here the CD45-CD31-CD29+mEF-SK4+PDGFRα+Sca-1+periostin+ (Sca-1+) cardiac fibroblast subset as the main GM-CSF producer in both experimental autoimmune myocarditis and myocardial infarction mouse models. Specific ablation of IL-17A signaling to Sca-1+periostin+ cardiac fibroblasts (PostnCreIl17rafl/fl) protected mice from post-infarct heart failure and death. Moreover, PostnCreIl17rafl/fl mice had significantly fewer GM-CSF-producing Sca-1+ cardiac fibroblasts and inflammatory Ly6Chi monocytes in the heart. Sca-1+ cardiac fibroblasts were not only potent GM-CSF producers, but also exhibited plasticity and switched their cytokine production profiles depending on local microenvironments. Moreover, we also found GM-CSF-positive cardiac fibroblasts in cardiac biopsy samples from heart failure patients of myocarditis or ischemic origin. Thus, this is the first identification of a pathological GM-CSF-producing cardiac fibroblast subset in human and mice hearts with myocarditis and ischemic cardiomyopathy. Sca-1+ cardiac fibroblasts direct the type of immune cells infiltrating the heart during cardiac inflammation and drive the development of heart failure.

Original languageEnglish (US)
JournalEuropean Journal of Immunology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Granulocyte-Macrophage Colony-Stimulating Factor
Heart Failure
Fibroblasts
Myocarditis
Interleukin-17
Inflammation
Cardiomyopathies
Monocytes
Myocardial Infarction
Cytokines
Biopsy

Keywords

  • Fibroblasts
  • GM-CSF
  • Heart failure
  • IL-17
  • Myocarditis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Chen, G., Bracamonte-Baran, W., Diny, N. L., Hou, X., Talor, M. V., Fu, K., ... Čiháková, D. (Accepted/In press). Sca-1+ cardiac fibroblasts promote development of heart failure. European Journal of Immunology. https://doi.org/10.1002/eji.201847583

Sca-1+ cardiac fibroblasts promote development of heart failure. / Chen, Guobao; Bracamonte-Baran, William; Diny, Nicola L.; Hou, Xuezhou; Talor, Monica V.; Fu, Kai; Liu, Yue; Davogustto, Giovanni; Vasquez, Hernan; Taegtmeyer, Heinrich; Frazier, O. Howard; Waisman, Ari; Conway, Simon; Wan, Fengyi; Čiháková, Daniela.

In: European Journal of Immunology, 01.01.2018.

Research output: Contribution to journalArticle

Chen, G, Bracamonte-Baran, W, Diny, NL, Hou, X, Talor, MV, Fu, K, Liu, Y, Davogustto, G, Vasquez, H, Taegtmeyer, H, Frazier, OH, Waisman, A, Conway, S, Wan, F & Čiháková, D 2018, 'Sca-1+ cardiac fibroblasts promote development of heart failure', European Journal of Immunology. https://doi.org/10.1002/eji.201847583
Chen, Guobao ; Bracamonte-Baran, William ; Diny, Nicola L. ; Hou, Xuezhou ; Talor, Monica V. ; Fu, Kai ; Liu, Yue ; Davogustto, Giovanni ; Vasquez, Hernan ; Taegtmeyer, Heinrich ; Frazier, O. Howard ; Waisman, Ari ; Conway, Simon ; Wan, Fengyi ; Čiháková, Daniela. / Sca-1+ cardiac fibroblasts promote development of heart failure. In: European Journal of Immunology. 2018.
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AU - Fu, Kai

AU - Liu, Yue

AU - Davogustto, Giovanni

AU - Vasquez, Hernan

AU - Taegtmeyer, Heinrich

AU - Frazier, O. Howard

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AU - Conway, Simon

AU - Wan, Fengyi

AU - Čiháková, Daniela

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