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Conventional Dendritic Cells Impair Recovery after Myocardial Infarction

Ischemic myocardial injury results in sterile cardiac inflammation that leads to tissue repair, two processes controlled by mononuclear phagocytes. Despite global burden of cardiovascular diseases, we do not understand the functional contribution to pathogenesis of specific cardiac mononuclear phago...

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Published in:The Journal of immunology (1950) 2018-09, Vol.201 (6), p.1784-1798
Main Authors: Lee, Jun Seong, Jeong, Se-Jin, Kim, Sinai, Chalifour, Lorraine, Yun, Tae Jin, Miah, Mohammad Alam, Li, Bin, Majdoubi, Abdelilah, Sabourin, Antoine, Keler, Tibor, Guimond, Jean V, Haddad, Elie, Choi, Eui-Young, Epelman, Slava, Choi, Jae-Hoon, Thibodeau, Jacques, Oh, Goo Taeg, Cheong, Cheolho
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Language:English
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Summary:Ischemic myocardial injury results in sterile cardiac inflammation that leads to tissue repair, two processes controlled by mononuclear phagocytes. Despite global burden of cardiovascular diseases, we do not understand the functional contribution to pathogenesis of specific cardiac mononuclear phagocyte lineages, in particular dendritic cells. To address this limitation, we used detailed lineage tracing and genetic studies to identify bona fide murine and human CD103 conventional dendritic cell (cDC)1s, CD11b cDC2s, and plasmacytoid DCs (pDCs) in the heart of normal mice and immunocompromised NSG mice reconstituted with human CD34 cells, respectively. After myocardial infarction (MI), the specific depletion of cDCs, but not pDCs, improved cardiac function and prevented adverse cardiac remodeling. Our results showed that fractional shortening measured after MI was not influenced by the absence of pDCs. Interestingly, however, depletion of cDCs significantly improved reduction in fractional shortening. Moreover, fibrosis and cell areas were reduced in infarcted zones. This correlated with reduced numbers of cardiac macrophages, neutrophils, and T cells, indicating a blunted inflammatory response. Accordingly, mRNA levels of proinflammatory cytokines IL-1β and IFN-γ were reduced. Collectively, our results demonstrate the unequivocal pathological role of cDCs following MI.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1800322