The role of Interleukin-3 in autoimmune myocarditis

• Applicant: Dr. Henrike Janssen
• Subject Area: Anaesthesiology
• Term: from 2019 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 420580046

Myocarditis is the leading cause of heart failure predominantly in males under the age of 40. The majority of cases are based on infections, dominated by Coxsackievirus B3 in Europe and North America. Although half of infections will resolve within 4 weeks, up to 30% of patients will reach a chronic stage, ending in dilated cardiomyopathy (DCM). Diagnosis is difficult, with endomyocardial biopsy being considered the gold standard. Where no viral genome, but histopathological signs of myocarditis can be detected, diagnosis of autoimmune myocarditis needs to be taken into account. For all subtypes of myocarditis, therapy includes symptom control of arrhythmias and heart failure. Potential immunomodulatory, as well immunosuppressive therapies are investigated. However, with incomplete understanding of the pathomechanism these lack specificity. There is evidence that autoimmune myocarditis is mediated by T cells. After viral infection and potential resolution, autoimmunity develops because the virus shares epitopes with cardiac proteins, and because infection may cause damage to cardiomyocytes, exposing autoantigens. The role of interleukin-3, and its potential impact on a T cell mediated inflammatory cascade in myocarditis, has not been elucidated. Preliminary data by the host lab states that interleukin-3 knockout mice show less myocardial inflammation, specifically less influx of leukocytes, and less myocardial damage than the referring wildtype in a model of myocarditis. Patients suffering myocarditis have more expression of interleukin-3 in the myocardium, suggesting a crucial role in humans as well. In the proposed project, I will investigate how the absence of interleukin-3 impacts upon the inflammatory profile of leukocytes in a murine model of autoimmune myocarditis. I will explore the source of interleukin-3 by organ and cell type and, finally, examine the impact of a systemic interleukin-3 block as a potential target for immunomodulatory therapy. The insights from this project may lead to new treatment strategies for myocarditis.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Filip Swirski, Ph.D.