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Myocarditis Elicits Dendritic Cell and Monocyte Infiltration in the Heart and Self-Antigen Presentation by Conventional Type 2 Dendritic Cells
- Source :
- Frontiers in Immunology, Vol 9 (2018), Frontiers in Immunology, 9:2714. Frontiers Media S.A., Frontiers in Immunology, FRONTIERS IN IMMUNOLOGY
- Publication Year :
- 2018
- Publisher :
- Frontiers Media S.A., 2018.
-
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.
- Subjects :
- EXPERIMENTAL AUTOIMMUNE MYOCARDITIS
0301 basic medicine
heart failure
medicine.disease_cause
Autoantigens
Monocytes
Autoimmunity
ACTIVATION
Mice
Medicine and Health Sciences
autoreactive
Immunology and Allergy
Medicine
MACROPHAGES
Original Research
Antigen Presentation
Mice, Inbred BALB C
autoimmunity
CD4 T-CELLS
Cell Differentiation
medicine.anatomical_structure
MOUSE BONE-MARROW
ALPHA-MYOSIN
Cardiomyopathy, Dilated
lcsh:Immunologic diseases. Allergy
STEADY-STATE
RAT-HEART
Myocarditis
Immunology
Antigen presentation
T cells
autoreactive T cells
Mice, Transgenic
Autoimmune Diseases
03 medical and health sciences
Antigen
APOPTOTIC CELLS
Animals
dendritic cells
Antigen-presenting cell
business.industry
Monocyte
T-cell receptor
Biology and Life Sciences
Dendritic cell
Th1 Cells
DILATED CARDIOMYOPATHY
medicine.disease
030104 developmental biology
Th17 Cells
myocarditis
business
lcsh:RC581-607
Subjects
Details
- ISSN :
- 16643224
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....76f24d92241ba3cb97c9fcc8331b0531