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Myocarditis elicits dendritic cell and monocyte infiltration in the heart and self-antigen presentation by conventional type 2 dendritic cells

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Abstract
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 (ARC) triggers autoimmunity. Experimental autoimmune myocarditis (EAM) was induced by immunizing mice with alpha-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 alpha-myosin loaded GM-cDC2s could induce EAM. We also studied antigen presenting capacity of endogenous type 1 CD24(+) cDCs (cDC1s), cDC2s, and MCs for alpha-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 alpha-myosin to TCR-M cells and induced Th1/Th17 differentiation. Loss of IRF4 in lrf4(fl)(/)(fl).Cd11 cCre mice reduced MHCII expression on GM-cDC2s in vitro and cDC2 migration in vivo. However, partly defective cDC2 functions in lrf4(fl)(/)(fl).Cd11 cCre 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
EXPERIMENTAL AUTOIMMUNE MYOCARDITIS, MOUSE BONE-MARROW, CD4 T-CELLS, DILATED CARDIOMYOPATHY, APOPTOTIC CELLS, STEADY-STATE, ALPHA-MYOSIN, RAT-HEART, MACROPHAGES, ACTIVATION, dendritic cells, myocarditis, autoimmunity, heart failure, autoreactive, T cells

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Citation

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Chicago
Van Der Borght, Katrien, Charlotte Scott, Liesbet Martens, Dorine Sichien, Gert Van Isterdael, Veronika Nindl, Yvan Saeys, et al. 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.
APA
Van Der Borght, K., Scott, C., Martens, L., Sichien, D., Van Isterdael, G., Nindl, V., Saeys, Y., et al. (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.
Vancouver
1.
Van Der Borght K, Scott C, Martens L, Sichien D, Van Isterdael G, Nindl V, et al. Myocarditis elicits dendritic cell and monocyte infiltration in the heart and self-antigen presentation by conventional type 2 dendritic cells. FRONTIERS IN IMMUNOLOGY. 2018;9.
MLA
Van Der Borght, Katrien et al. “Myocarditis Elicits Dendritic Cell and Monocyte Infiltration in the Heart and Self-antigen Presentation by Conventional Type 2 Dendritic Cells.” FRONTIERS IN IMMUNOLOGY 9 (2018): n. pag. Print.
@article{8600862,
  abstract     = {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 (ARC) triggers autoimmunity. Experimental autoimmune myocarditis (EAM) was induced by immunizing mice with alpha-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 alpha-myosin loaded GM-cDC2s could induce EAM. We also studied antigen presenting capacity of endogenous type 1 CD24(+) cDCs (cDC1s), cDC2s, and MCs for alpha-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 alpha-myosin to TCR-M cells and induced Th1/Th17 differentiation. Loss of IRF4 in lrf4(fl)(/)(fl).Cd11 cCre mice reduced MHCII expression on GM-cDC2s in vitro and cDC2 migration in vivo. However, partly defective cDC2 functions in lrf4(fl)(/)(fl).Cd11 cCre 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.},
  articleno    = {2714},
  author       = {Van Der Borght, Katrien and Scott, Charlotte and Martens, Liesbet and Sichien, Dorine and Van Isterdael, Gert and Nindl, Veronika and Saeys, Yvan and Boon, Louis and Ludewig, Burkhard and Gillebert, Thierry and Lambrecht, Bart},
  issn         = {1664-3224},
  journal      = {FRONTIERS IN IMMUNOLOGY},
  language     = {eng},
  pages        = {14},
  title        = {Myocarditis elicits dendritic cell and monocyte infiltration in the heart and self-antigen presentation by conventional type 2 dendritic cells},
  url          = {http://dx.doi.org/10.3389/fimmu.2018.02714},
  volume       = {9},
  year         = {2018},
}

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