Conventional Dendritic Cells Impair Recovery after Myocardial Infarction.

Abstract

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.

• Authors: Jun Seong Lee, Se-Jin Jeong, Sinai Kim, Lorraine Chalifour, Tae Jin Yun, Mohammad Alam Miah, Bin Li, Abdelilah Majdoubi, Antoine Sabourin, Tibor Keler, Jean V Guimond, Elie Haddad, Eui-Young Choi, Slava Epelman, Jae-Hoon Choi, Jacques Thibodeau, Goo Taeg Oh, Cheolho Cheong
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 201 Issue 6 Pg. 1784-1798 (09 15 2018) ISSN: 1550-6606 [Electronic] United States
• PMID: 30097529 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 by The American Association of Immunologists, Inc.

Chemical References

• IFNG protein, human
• IFNG protein, mouse
• IL1B protein, human
• IL1B protein, mouse
• Interleukin-1beta
• Interferon-gamma

Topics

• Animals
• Cell Movement (genetics, immunology)
• Dendritic Cells (immunology, pathology)
• Humans
• Interferon-gamma (genetics, immunology)
• Interleukin-1beta (genetics, immunology)
• Macrophages (immunology, pathology)
• Mice
• Mice, Knockout
• Monocytes (immunology, pathology)
• Myocardial Infarction (genetics, immunology, pathology)
• Neutrophils (immunology, pathology)
• T-Lymphocytes (immunology, pathology)