title: Dectin-2 Deficiency Modulates Th1 Differentiation and Improves Wound Healing After Myocardial Infarction.
abstract: BACKGROUND
  Macrophages are involved in wound healing after myocardial infarction (MI). The role of Dectin-2, a pattern recognition receptor mainly expressed on myeloid cells, in the infarct healing remains unknown.
  
  
  OBJECTIVE
  The aim of this study is to determine whether Dectin-2 signaling is involved in the healing process and cardiac remodeling after MI and to elucidate the underlying molecular mechanisms.
  
  
  RESULTS
  In a mouse model of permanent coronary ligation, Dectin-2, mainly expressed in macrophages, was shown to be increased in the early phase after MI. Dectin-2 knockout mice showed an improvement in the infarct healing and cardiac remodeling, compared with wild-type mice, which was demonstrated by significantly lower mortality because of cardiac rupture, increased wall thickness, and better cardiac function. Increased expression of α-smooth muscle actin and collagen I/III was observed, whereas the levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 were decreased in the hearts of Dectin-2 knockout mice after MI. Dectin-2 deficiency inhibited the rate of apoptotic and necrotic cell death. However, Dectin-2 did not affect immune cell infiltration and macrophage polarization, but it led to a stronger activation of the Th1/interferon-γ immune reaction, through the enhancement of interleukin-12 production in the heart. Interferon-γ was shown to downregulate transforming growth factor-β-induced expression of α-smooth muscle actin and collagen I/III in isolated cardiac fibroblasts, leading to a decrease in migration and myofibroblast differentiation. Finally, Dectin-2 knockout improved myocardial ischemia-reperfusion injury and infarct healing.
  
  
  CONCLUSIONS
  Dectin-2 leads to an increase in cardiac rupture, impairs wound healing, and aggravates cardiac remodeling after MI through the modulation of Th1 differentiation.
authors.affiliation: From the Department of Cardiology, Rui Jin Hospital (X.Y., H.Z., Q.F., J.H., R.T., W.S., L.L., Q.Z., R.Z.) and Institute of Cardiovascular Diseases (X.Y., H.Z., Q.F., Q.C., L.L.), Shanghai Jiaotong University School of Medicine, PR China; and Division of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan (Y.I.).
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Yan
authors.affiliation: From the Department of Cardiology, Rui Jin Hospital (X.Y., H.Z., Q.F., J.H., R.T., W.S., L.L., Q.Z., R.Z.) and Institute of Cardiovascular Diseases (X.Y., H.Z., Q.F., Q.C., L.L.), Shanghai Jiaotong University School of Medicine, PR China; and Division of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan (Y.I.).
authors.forename: Hang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: From the Department of Cardiology, Rui Jin Hospital (X.Y., H.Z., Q.F., J.H., R.T., W.S., L.L., Q.Z., R.Z.) and Institute of Cardiovascular Diseases (X.Y., H.Z., Q.F., Q.C., L.L.), Shanghai Jiaotong University School of Medicine, PR China; and Division of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan (Y.I.).
authors.forename: Qin
authors.initials: Q
authors.lastname: Fan
authors.affiliation: From the Department of Cardiology, Rui Jin Hospital (X.Y., H.Z., Q.F., J.H., R.T., W.S., L.L., Q.Z., R.Z.) and Institute of Cardiovascular Diseases (X.Y., H.Z., Q.F., Q.C., L.L.), Shanghai Jiaotong University School of Medicine, PR China; and Division of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan (Y.I.).
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
authors.affiliation: From the Department of Cardiology, Rui Jin Hospital (X.Y., H.Z., Q.F., J.H., R.T., W.S., L.L., Q.Z., R.Z.) and Institute of Cardiovascular Diseases (X.Y., H.Z., Q.F., Q.C., L.L.), Shanghai Jiaotong University School of Medicine, PR China; and Division of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan (Y.I.).
authors.forename: Rong
authors.initials: R
authors.lastname: Tao
authors.affiliation: From the Department of Cardiology, Rui Jin Hospital (X.Y., H.Z., Q.F., J.H., R.T., W.S., L.L., Q.Z., R.Z.) and Institute of Cardiovascular Diseases (X.Y., H.Z., Q.F., Q.C., L.L.), Shanghai Jiaotong University School of Medicine, PR China; and Division of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan (Y.I.).
authors.forename: Qiujing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: From the Department of Cardiology, Rui Jin Hospital (X.Y., H.Z., Q.F., J.H., R.T., W.S., L.L., Q.Z., R.Z.) and Institute of Cardiovascular Diseases (X.Y., H.Z., Q.F., Q.C., L.L.), Shanghai Jiaotong University School of Medicine, PR China; and Division of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan (Y.I.).
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: From the Department of Cardiology, Rui Jin Hospital (X.Y., H.Z., Q.F., J.H., R.T., W.S., L.L., Q.Z., R.Z.) and Institute of Cardiovascular Diseases (X.Y., H.Z., Q.F., Q.C., L.L.), Shanghai Jiaotong University School of Medicine, PR China; and Division of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan (Y.I.).
authors.forename: Weifeng
authors.initials: W
authors.lastname: Shen
authors.affiliation: From the Department of Cardiology, Rui Jin Hospital (X.Y., H.Z., Q.F., J.H., R.T., W.S., L.L., Q.Z., R.Z.) and Institute of Cardiovascular Diseases (X.Y., H.Z., Q.F., Q.C., L.L.), Shanghai Jiaotong University School of Medicine, PR China; and Division of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan (Y.I.).
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: From the Department of Cardiology, Rui Jin Hospital (X.Y., H.Z., Q.F., J.H., R.T., W.S., L.L., Q.Z., R.Z.) and Institute of Cardiovascular Diseases (X.Y., H.Z., Q.F., Q.C., L.L.), Shanghai Jiaotong University School of Medicine, PR China; and Division of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan (Y.I.).
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: From the Department of Cardiology, Rui Jin Hospital (X.Y., H.Z., Q.F., J.H., R.T., W.S., L.L., Q.Z., R.Z.) and Institute of Cardiovascular Diseases (X.Y., H.Z., Q.F., Q.C., L.L.), Shanghai Jiaotong University School of Medicine, PR China; and Division of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan (Y.I.). zhangruiyan@263.net.
authors.forename: Ruiyan
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D038041:Lymphopoiesis; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D000199:Actins; D037181:Lectins, C-Type; C544013:alpha-smooth muscle actin, mouse; C445340:dectin-2, mouse; D007371:Interferon-gamma; D003094:Collagen; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Th1 cells; collagen; flow cytometry; myocardial infarction; wound healing