Van der Borght K Scott CL Martens L Sichien D Van Isterdael G Nindl V Saeys Y Boon L Ludewig B Gillebert TC Lambrecht BN 2018 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. application/pdf https://sonar.ch/global/documents/268778 eng info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.02714 info:eu-repo/semantics/altIdentifier/pmid/30524444 info:eu-repo/semantics/openAccess 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 Myocarditis Elicits Dendritic Cell and Monocyte Infiltration in the Heart and Self-Antigen Presentation by Conventional Type 2 Dendritic Cells. http://purl.org/coar/resource_type/c_6501