Conventional Dendritic Cells Impair Recovery after Myocardial Infarction

• Published in: The Journal of immunology (1950) Vol. 201; no. 6; pp. 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
• Format: Journal Article
• Language: English
• Published: United States 15-09-2018
• Subjects: Animals; Cell Movement - genetics; Cell Movement - immunology; Dendritic Cells - immunology; Dendritic Cells - pathology; Humans; Interferon-gamma - genetics; Interferon-gamma - immunology; Interleukin-1beta - genetics; Interleukin-1beta - immunology; Macrophages - immunology; Macrophages - pathology; Mice; Mice, Knockout; Monocytes - immunology; Monocytes - pathology; Myocardial Infarction - genetics; Myocardial Infarction - immunology; Myocardial Infarction - pathology; Neutrophils - immunology; Neutrophils - pathology; T-Lymphocytes - immunology; T-Lymphocytes - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1800322

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.