Conventional Dendritic Cells Impair Recovery after Myocardial Infarction.
Jun Seong LeeSe-Jin JeongSinai KimLorraine ChalifourTae Jin YunMohammad Alam MiahBin LiAbdelilah MajdoubiAntoine SabourinTibor KelerJean V GuimondElie HaddadEui Young ChoiSlava EpelmanJae-Hoon ChoiJacques ThibodeauGoo Taeg OhCheolho CheongPublished in: Journal of immunology (Baltimore, Md. : 1950) (2018)
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.
Keyphrases
- dendritic cells
- immune response
- regulatory t cells
- left ventricular
- inflammatory response
- endothelial cells
- cardiovascular disease
- peripheral blood
- single cell
- heart failure
- induced pluripotent stem cells
- pluripotent stem cells
- stem cells
- type diabetes
- emergency department
- genome wide
- metabolic syndrome
- cell therapy
- mesenchymal stem cells
- cell proliferation
- gene expression
- bone marrow
- risk factors
- dna methylation
- cardiovascular events
- acute respiratory distress syndrome
- mechanical ventilation
- adverse drug
- binding protein