Conventional Dendritic Cells Impair Recovery after Myocardial Infarction
- 주제(기타) Immunology
- 설명문(일반) [Lee, Jun Seong; Miah, Mohammad Alam; Li, Bin; Majdoubi, Abdelilah; Sabourin, Antoine; Haddad, Elie; Thibodeau, Jacques; Cheong, Cheolho] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ H3T 1J4, Canada; [Lee, Jun Seong; Yun, Tae Jin; Miah, Mohammad Alam; Cheong, Cheolho] Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada; [Lee, Jun Seong; Majdoubi, Abdelilah; Sabourin, Antoine; Thibodeau, Jacques] Univ Montreal, Lab Immunol Mol, Montreal, PQ H3T 1J4, Canada; [Jeong, Se-Jin; Kim, Sinai; Oh, Goo Taeg] Ewha Womans Univ, Dept Life Sci, Natl Creat Initiat, Immune & Vasc Cell Network Res Ctr, Seoul 120750, South Korea; [Chalifour, Lorraine] McGill Univ, Lady Davis Inst, Div Expt Med, Montreal, PQ H3T 1E2, Canada; [Yun, Tae Jin; Cheong, Cheolho] McGill Univ, Div Expt Med, Dept Med, Montreal, PQ H4A 3J1, Canada; [Li, Bin] Univ Montreal, Dept Biol Mol, Montreal, PQ H3T 1J4, Canada; [Keler, Tibor] Celldex Therapeut, Hampton, NJ 08827 USA; [Guimond, Jean V.] Ctr Sante & Serv Sociaux Jeanne Mance, Montreal, PQ H2T 2R9, Canada; [Haddad, Elie] Ctr Hosp Univ St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada; [Choi, Eui-Young] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Seoul 06273, South Korea; [Epelman, Slava] Peter Munk Cardiac Ctr, Toronto, ON M5G 2N2, Canada; [Epelman, Slava] Ted Rogers Ctr Heart Res, Toronto, ON M5G 1X8, Canada; [Epelman, Slava] Univ Hlth Network, Toronto Gen Hosp, Res Inst, Toronto, ON M5G 2C4, Canada; [Choi, Jae-Hoon] Hanyang Univ, Res Inst Nat Sci, Coll Nat Sci, Dept Life Sci, Seoul 04763, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 AMER ASSOC IMMUNOLOGISTS
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000156108
- 본문언어 영어
- Published As http://dx.doi.org/10.4049/jimmunol.1800322
초록/요약
Ischemic myocardial injury results in sterile cardiac inflammation that leads to tissue repair, two processes controlled by mono-nuclear 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-1 beta and IFN-gamma were reduced. Collectively, our results demonstrate the unequivocal pathological role of cDCs following MI.
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