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Published on: June 18, 2016
Coronin 1 deficiency protects from the development of autoimmune myocarditis by reducing CD4+ T cells
Amanda Ochoa-Espinosa1, Lucile Genty1, Lifen Xu1
1Department of Biomedicine, University of Basel, Basel, Switzerland.
Insights
Mice lacking coronin 1 showed reduced experimental autoimmune myocarditis (EAM) severity due to fewer CD4+ T cells. This protection, linked to increased IL-10, suggests coronin 1 deficiency is beneficial in autoimmune heart disease.
Area of Science:
- Immunology
- Cardiology
- Molecular Biology
Background:
- Dilated cardiomyopathy (DCM) is a major cause of heart failure, often linked to viral or autoimmune myocarditis.
- CD4+ T cells are critical in autoimmune myocarditis pathogenesis.
- Coronin 1 is essential for peripheral T cell survival, making it a potential therapeutic target.
Purpose of the Study:
- To investigate the role of coronin 1 in experimental autoimmune myocarditis (EAM).
- To determine if coronin 1 deficiency protects against EAM development.
- To explore the underlying mechanisms, including CD4+ T cell involvement and IL-10 levels.
Main Methods:
- Experimental autoimmune myocarditis (EAM) was induced in coronin 1-deficient and wild-type (WT) mice.
- CD4+ T cell transfer and IL-10 blockade were performed in subsets of mice.
- Echocardiography, histological scoring, leukocyte analysis, cytokine measurement (including IL-10), and RNA sequencing were conducted.
Main Results:
- Coronin 1-deficient mice exhibited significantly lower myocarditis severity and reduced myocardial inflammatory cell infiltration compared to WT mice.
- Plasma IL-10 levels were selectively increased in coronin 1-deficient mice.
- Transfer of WT CD4+ T cells restored EAM, while IL-10 blockade did not prevent disease development.
Conclusions:
- Coronin 1 deficiency protects against EAM by reducing CD4+ T cell infiltration, leading to less cardiac structural damage.
- Increased IL-10 in coronin 1-deficient mice may contribute to protection, but is not solely responsible for preventing EAM.
- Targeting coronin 1 could be a novel strategy for treating autoimmune myocarditis and preventing heart failure.
Aims:
Dilated cardiomyopathy (DCM) caused by viral myocarditis and autoimmune processes is a frequent cause for heart failure. CD4+ T cells are indispensable for autoimmune myocarditis. Coronin 1 is required for peripheral T cell survival. We therefore hypothesized that deficiency in coronin 1 protects mice from experimental autoimmune myocarditis (EAM).
Methods:
EAM was induced in coronin 1-deficient and wild-type (WT) mice. WT CD4+ T cells isolated from spleens were transferred to coronin 1-deficient mice in a subset of animals; IL-10 was blocked in another subset before EAM induction. On day 21 mice underwent echocardiography and were sacrificed. Myocarditis severity was scored (Grades 0-4) on histology. Leukocyte fractions in blood and heart tissue were characterized. Plasma cytokines including interleukin (IL)-10 were measured and RNA sequencing of myocardial tissue was performed.
Results:
The severity of myocarditis was lower in coronin 1-deficient versus WT mice [median 0 (25th-75th percentile 0-2) vs. 4 (3-4), P < 0.0001]. Coronin 1-deficient animals showed significant reductions of inflammatory cells in the myocardium [median 2.5% (25th-75th percentile 1.5%-7.0%) vs. 28.3% (14.5%-54.8%), P < 0.0001]. IL-10 was selectively increased in the plasma of coronin 1-deficient mice [median 3.0 pg/mL (25th-75th percentile 1.3-5.2 pg/mL) vs. 0.4 pg/mL (0-2.0 pg/mL), P < 0.05]. Transfer of WT CD4+ T cells but not blocking of IL-10 restored EAM. Left ventricular mass was increased, but effects of myocarditis on left ventricular function were evident only on the RNA level.
Conclusions:
Deficiency in coronin 1 protects from the development of EAM by reducing CD4+ T cells. This protection resulted in less structural alterations of the left ventricular myocardium. IL-10 was selectively increased in the plasma of coronin 1-deficient mice, but blocking of IL-10 was not sufficient to restore EAM.
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