title: Role of bone marrow-derived CD11c+dendritic cells in systolic overload-induced left ventricular inflammation, fibrosis and hypertrophy.
abstract: Inflammatory responses play an important role in the development of left ventricular (LV) hypertrophy and dysfunction. Recent studies demonstrated that increased T-cell infiltration and T-cell activation contribute to LV hypertrophy and dysfunction. Dendritic cells (DCs) are professional antigen-presenting cells that orchestrate immune responses, especially by modulating T-cell function. In this study, we investigated the role of bone marrow-derived CD11c+DCs in transverse aortic constriction (TAC)-induced LV fibrosis and hypertrophy in mice. We observed that TAC increased the number of CD11c+cells and the percentage of CD11c+MHCII+(major histocompatibility complex class II molecule positive) DCs in the LV, spleen and peripheral blood in mice. Using bone marrow chimeras and an inducible CD11c+DC ablation model, we found that depletion of bone marrow-derived CD11c+DCs significantly attenuated LV fibrosis and hypertrophy in mice exposed to 24 weeks of moderate TAC. CD11c+DC ablation significantly reduced TAC-induced myocardial inflammation as indicated by reduced myocardial CD45+cells, CD11b+cells, CD8+T cells and activated effector CD8+CD44+T cells in LV tissues. Moreover, pulsing of autologous DCs with LV homogenates from TAC mice promoted T-cell proliferation. These data indicate that bone marrow-derived CD11c+DCs play a maladaptive role in hemodynamic overload-induced cardiac inflammation, hypertrophy and fibrosis through the presentation of cardiac self-antigens to T cells.
authors.affiliation: Cardiovascular Division and Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Cardiovascular Division and Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Kwak
authors.affiliation: Department of Pharmacology and Toxicology, University of Graz, Graz, Austria.
authors.forename: John
authors.initials: J
authors.lastname: Fassett
authors.affiliation: Shanxi Provincial People's Hospital, Taiyuan, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Cardiovascular Division and Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
authors.forename: Wu
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Cardiology, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Weng
authors.affiliation: Cardiovascular Division and Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Cardiovascular Division and Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bache
authors.affiliation: Division of Rheumatic and Autoimmune Diseases, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Mueller
authors.affiliation: Cardiovascular Division and Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, MN, 55455, USA. chenx106@umn.edu.|Lillehei Heart Institute, University of Minnesota, Cancer and Cardiovascular Research Building (CCRB), 2231 6th Street SE, 4-135, Minneapolis, MN, 55455, USA. chenx106@umn.edu.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006332:Cardiomegaly / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D017379:Hypertrophy, Left Ventricular / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000276:immunology; D020257:Ventricular Remodeling / Q000276:immunology*
chemical_list: D039521:CD11c Antigen
keywords: Dendritic cells; Fibrosis; Hypertrophy; Inflammation; Left ventricle