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Myocarditis Elicits Dendritic Cell and Monocyte Infiltration in the Heart and Self-Antigen Presentation by Conventional Type 2 Dendritic Cells.

  • Van der Borght K Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
  • Scott CL Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
  • Martens L Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
  • Sichien D Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
  • Van Isterdael G Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
  • Nindl V Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Saeys Y Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
  • Boon L Bioceros, Utrecht, Netherlands.
  • Ludewig B Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Gillebert TC Department of Internal Medicine, Ghent University, Ghent, Belgium.
  • Lambrecht BN Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
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  • 2018-12-08
Published in:
  • Frontiers in immunology. - 2018
autoimmunity
autoreactive T cells
dendritic cells
heart failure
myocarditis
Animals
Antigen Presentation
Autoantigens
Autoimmune Diseases
Cardiomyopathy, Dilated
Cell Differentiation
Dendritic Cells
Mice
Mice, Inbred BALB C
Mice, Transgenic
Monocytes
Myocarditis
Th1 Cells
Th17 Cells
English Autoimmune myocarditis often leads to dilated cardiomyopathy (DCM). Although T cell reactivity to cardiac self-antigen is common in the disease, it is unknown which antigen presenting cell (APC) triggers autoimmunity. Experimental autoimmune myocarditis (EAM) was induced by immunizing mice with α-myosin loaded bone marrow APCs cultured in GM-CSF. APCs found in such cultures include conventional type 2 CD11b+ cDCs (GM-cDC2s) and monocyte-derived cells (GM-MCs). However, only α-myosin loaded GM-cDC2s could induce EAM. We also studied antigen presenting capacity of endogenous type 1 CD24+ cDCs (cDC1s), cDC2s, and MCs for α-myosin-specific TCR-transgenic TCR-M CD4+ T cells. After EAM induction, all cardiac APCs significantly increased and cDCs migrated to the heart-draining mediastinal lymph node (LN). Primarily cDC2s presented α-myosin to TCR-M cells and induced Th1/Th17 differentiation. Loss of IRF4 in Irf4 .Cd11cCre mice reduced MHCII expression on GM-cDC2s in vitro and cDC2 migration in vivo. However, partly defective cDC2 functions in Irf4 .Cd11cCre mice did not suppress EAM. MCs were the largest APC subset in the inflamed heart and produced pro-inflammatory cytokines. Targeting APC populations could be exploited in the design of new therapies for cardiac autoimmunity.
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  • English
Open access status
gold
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https://sonar.ch/global/documents/268778
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