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 α-my...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02714/full |
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| author | Katrien Van der Borght Katrien Van der Borght Charlotte L. Scott Charlotte L. Scott Liesbet Martens Liesbet Martens Liesbet Martens Dorine Sichien Dorine Sichien Gert Van Isterdael Gert Van Isterdael Gert Van Isterdael Veronika Nindl Yvan Saeys Yvan Saeys Louis Boon Burkhard Ludewig Thierry C. Gillebert Bart N. Lambrecht Bart N. Lambrecht Bart N. Lambrecht |
| author_facet | Katrien Van der Borght Katrien Van der Borght Charlotte L. Scott Charlotte L. Scott Liesbet Martens Liesbet Martens Liesbet Martens Dorine Sichien Dorine Sichien Gert Van Isterdael Gert Van Isterdael Gert Van Isterdael Veronika Nindl Yvan Saeys Yvan Saeys Louis Boon Burkhard Ludewig Thierry C. Gillebert Bart N. Lambrecht Bart N. Lambrecht Bart N. Lambrecht |
| author_sort | Katrien Van der Borght |
| collection | DOAJ |
| description | 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 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. |
| first_indexed | 2024-12-19T21:05:21Z |
| format | Article |
| id | doaj.art-e8759fe85a3d4d62b5da07e577ad6ce4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T21:05:21Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e8759fe85a3d4d62b5da07e577ad6ce42022-12-21T20:05:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02714389684Myocarditis Elicits Dendritic Cell and Monocyte Infiltration in the Heart and Self-Antigen Presentation by Conventional Type 2 Dendritic CellsKatrien Van der Borght0Katrien Van der Borght1Charlotte L. Scott2Charlotte L. Scott3Liesbet Martens4Liesbet Martens5Liesbet Martens6Dorine Sichien7Dorine Sichien8Gert Van Isterdael9Gert Van Isterdael10Gert Van Isterdael11Veronika Nindl12Yvan Saeys13Yvan Saeys14Louis Boon15Burkhard Ludewig16Thierry C. Gillebert17Bart N. Lambrecht18Bart N. Lambrecht19Bart N. Lambrecht20Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, BelgiumDepartment of Internal Medicine, Ghent University, Ghent, BelgiumImmunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, BelgiumDepartment of Biomedical Molecular Biology, Ghent University, Ghent, BelgiumImmunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, BelgiumDepartment of Internal Medicine, Ghent University, Ghent, BelgiumDepartment of Biomedical Molecular Biology, Ghent University, Ghent, BelgiumImmunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, BelgiumDepartment of Biomedical Molecular Biology, Ghent University, Ghent, BelgiumImmunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, BelgiumDepartment of Internal Medicine, Ghent University, Ghent, BelgiumDepartment of Biomedical Molecular Biology, Ghent University, Ghent, BelgiumInstitute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, SwitzerlandImmunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, BelgiumDepartment of Internal Medicine, Ghent University, Ghent, BelgiumBioceros, Utrecht, NetherlandsInstitute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, SwitzerlandDepartment of Internal Medicine, Ghent University, Ghent, BelgiumImmunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, BelgiumDepartment of Internal Medicine, Ghent University, Ghent, BelgiumDepartment of Pulmonary Medicine, Erasmus MC, Rotterdam, NetherlandsAutoimmune 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 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.02714/fulldendritic cellsmyocarditisautoimmunityheart failureautoreactive T cells |
| spellingShingle | Katrien Van der Borght Katrien Van der Borght Charlotte L. Scott Charlotte L. Scott Liesbet Martens Liesbet Martens Liesbet Martens Dorine Sichien Dorine Sichien Gert Van Isterdael Gert Van Isterdael Gert Van Isterdael Veronika Nindl Yvan Saeys Yvan Saeys Louis Boon Burkhard Ludewig Thierry C. Gillebert Bart N. Lambrecht Bart N. Lambrecht Bart N. Lambrecht Myocarditis Elicits Dendritic Cell and Monocyte Infiltration in the Heart and Self-Antigen Presentation by Conventional Type 2 Dendritic Cells Frontiers in Immunology dendritic cells myocarditis autoimmunity heart failure autoreactive T cells |
| title | Myocarditis Elicits Dendritic Cell and Monocyte Infiltration in the Heart and Self-Antigen Presentation by Conventional Type 2 Dendritic Cells |
| title_full | Myocarditis Elicits Dendritic Cell and Monocyte Infiltration in the Heart and Self-Antigen Presentation by Conventional Type 2 Dendritic Cells |
| title_fullStr | Myocarditis Elicits Dendritic Cell and Monocyte Infiltration in the Heart and Self-Antigen Presentation by Conventional Type 2 Dendritic Cells |
| title_full_unstemmed | Myocarditis Elicits Dendritic Cell and Monocyte Infiltration in the Heart and Self-Antigen Presentation by Conventional Type 2 Dendritic Cells |
| title_short | Myocarditis Elicits Dendritic Cell and Monocyte Infiltration in the Heart and Self-Antigen Presentation by Conventional Type 2 Dendritic Cells |
| title_sort | myocarditis elicits dendritic cell and monocyte infiltration in the heart and self antigen presentation by conventional type 2 dendritic cells |
| topic | dendritic cells myocarditis autoimmunity heart failure autoreactive T cells |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02714/full |
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