Imperial College London
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DrRashedaChowdhury

Faculty of Medicine, National Heart & Lung Institute

Advanced Research Fellow
 
 
 
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r.chowdhury

 
 
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ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Forte:2020:10.1161/CIRCULATIONAHA.120.044581,
author = {Forte, E and Perkins, B and Sintou, A and Kallkat, HS and Papanikolaou, A and Jenkins, C and Alsubaie, M and Chowdhury, RA and Duffy, TM and Skelly, DA and Branca, J and Bellahcene, M and Schneider, M and Harding, S and Furtado, MB and Ng, FS and Hasham, MG and Rosenthal, N and Sattler, S},
doi = {10.1161/CIRCULATIONAHA.120.044581},
journal = {Circulation},
pages = {821--836},
title = {Cross-priming dendritic cells exacerbate immunopathology after ischemic tissue damage in the heart},
url = {http://dx.doi.org/10.1161/CIRCULATIONAHA.120.044581},
volume = {143},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: Ischemic heart disease is a leading cause of heart failure and despite advanced therapeutic options, morbidity and mortality rates remain high. Although acute inflammation in response to myocardial cell death has been extensively studied, subsequent adaptive immune activity and anti-heart autoimmunity may also contribute to the development of HF. After ischemic injury to the myocardium, dendritic cells (DC) respond to cardiomyocyte necrosis, present cardiac antigen to T cells and potentially initiate a persistent autoimmune response against the heart. Cross-priming DC have the ability to activate both CD4+ helperand CD8+ cytotoxic T cells in response to necrotic cells and may thus be crucial players in exacerbating autoimmunity targeting the heart. This study investigates a role for cross priming DC in post-MI myocardial impairment through presentation of self-antigen fromnecrotic cardiomyocytes to cytotoxic CD8+ T cells.Methods: We induced type-2 myocardial infarction (MI)-like ischemic injury in the heart by treatment with a single high dose of the beta-adrenergic agonist isoproterenol. We characterized the DC population in the heart and mediastinal lymph nodes and analyzed long term cardiac immunopathology and functional decline in wild type and Clec9a-depleted mice lacking DC cross-priming function.Results: A diverse DC population, including cross-priming DC, is present in the heart and activated after ischemic injury. Clec9a -/- mice deficient in DC cross-priming are protected from long-term immune-mediated myocardial damage and decline of cardiac function, likely dueto dampened activation of cytotoxic CD8+ T cells.Conclusion: Activation of cytotoxic CD8+ T cells by cross-priming DC contributes to exacerbation of post-ischemic inflammatory damage of the myocardium and corresponding decline in cardiac function. Importantly, this provides novel therapeutic targets to prevent immune-mediated worsening of post-ischemic HF.
AU  - Forte,E
AU  - Perkins,B
AU  - Sintou,A
AU  - Kallkat,HS
AU  - Papanikolaou,A
AU  - Jenkins,C
AU  - Alsubaie,M
AU  - Chowdhury,RA
AU  - Duffy,TM
AU  - Skelly,DA
AU  - Branca,J
AU  - Bellahcene,M
AU  - Schneider,M
AU  - Harding,S
AU  - Furtado,MB
AU  - Ng,FS
AU  - Hasham,MG
AU  - Rosenthal,N
AU  - Sattler,S
DO  - 10.1161/CIRCULATIONAHA.120.044581
EP  - 836
PY  - 2020///
SN  - 0009-7322
SP  - 821
TI  - Cross-priming dendritic cells exacerbate immunopathology after ischemic tissue damage in the heart
T2  - Circulation
UR  - http://dx.doi.org/10.1161/CIRCULATIONAHA.120.044581
UR  - https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.044581
UR  - http://hdl.handle.net/10044/1/83798
VL  - 143
ER  -
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