Myocarditis elicits dendritic cell and monocyte infiltration in the heart and self-antigen presentation by conventional type 2 dendritic cells
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 a-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 a-myosin loaded GM-cDC2s could induce EAM. We also studied antigen presenting capacity of endogenous type 1 CD24+ cDCs (cDC1s), cDC2s, and MCs for a-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 a-myosin to TCR-M cells and induced Th1/Th17 differentiation. Loss of IRF4 in Irf4fl/fl.Cd11cCre mice reduced MHCII expression on GM-cDC2s in vitro and cDC2 migration in vivo. However, partly defective cDC2 functions in Irf4fl/fl.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.
|Keywords||Autoimmunity, Autoreactive T cells, Dendritic cells, Heart failure, Myocarditis|
|Persistent URL||dx.doi.org/10.3389/fimmu.2018.02714, hdl.handle.net/1765/112715|
|Journal||Frontiers in Immunology|
Van Der Borght, K. (Katrien), Scott, C.L, Martens, L, Sichien, D, Van Isterdael, G, Nindl, V. (Veronika), … Lambrecht, B.N.M. (2018). Myocarditis elicits dendritic cell and monocyte infiltration in the heart and self-antigen presentation by conventional type 2 dendritic cells. Frontiers in Immunology, 9(NOV). doi:10.3389/fimmu.2018.02714