Role of bone marrow-derived CD11c+ dendritic cells in systolic overload-induced left ventricular inflammation, fibrosis and hypertrophy

Huan Wang, Dongmin Kwak, John Fassett, Xiaohong Liu, Wu Yao, Xinyu Weng, Xin Xu, Yawei Xu, Robert J. Bache, Daniel L. Mueller, Yingjie Chen

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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.

Original languageEnglish (US)
Article number25
JournalBasic research in cardiology
Volume112
Issue number3
DOIs
StatePublished - May 1 2017

Bibliographical note

Publisher Copyright:
© 2017, Springer-Verlag Berlin Heidelberg.

Keywords

  • Dendritic cells
  • Fibrosis
  • Hypertrophy
  • Inflammation
  • Left ventricle

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