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

• Published in: Frontiers in immunology 2018-11, Vol.9, p.2714-2714
• Main Authors: Van der Borght, Katrien, Scott, Charlotte L, Martens, Liesbet, Sichien, Dorine, Van Isterdael, Gert, Nindl, Veronika, Saeys, Yvan, Boon, Louis, Ludewig, Burkhard, Gillebert, Thierry C, Lambrecht, Bart N
• Format: Article
• Language: English
• Subjects: autoimmunity; autoreactive T cells; dendritic cells; heart failure; Immunology; myocarditis
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.02714

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 mice reduced MHCII expression on GM-cDC2s and cDC2 migration . However, partly defective cDC2 functions in 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.