# Role of interleukin-3 in autoimmune and viral myocarditis

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2021 · $6,459

## Abstract

Myocarditis is a heterogeneous inflammatory disease of the heart muscle that constitutes a wide spectrum of
inflammatory pathologies. It can manifest from mild subclinical disease to severe outcomes, including
cardiogenic shock, life-threatening arrhythmias, and even sudden death. While many patients recover from
acute illness associated with myocarditis, the long-term sequelae of myocardial inflammation involves the
development of inflammatory dilated cardiomyopathy and chronic heart failure, both for which treatment
options are gravely limited. Given that myocarditis is such a highly polymorphic disease and specific clinical
guidelines for its treatment do not exist, it is important to identify common underlying mechanisms that drive
myocardial inflammation, in order to better prevent morbidity and mortality associated with myocarditis.
 To-date, most information regarding the pathogenesis of myocarditis has been gleaned from animal
models that mimic aspects of autoimmune and viral myocarditis. In these models, CD4+ T cells play a major
role in driving inflammation. However, it is still mechanistically unclear how various cytokines produced by
these cells can promote myocardial inflammation and disease progression to more serious and fatal outcomes.
Interestingly, our preliminary work suggests that interleukin (IL)-3, a cytokine from the colony-stimulating factor
(CSF) family, drives inflammation in the heart during the peak of experimental autoimmune myocarditis (EAM).
For example, we recently discovered that IL-3-deficient mice are protected from cardiac inflammation in EAM.
Upon profiling heart leukocytes, we found that IL-3 is specifically produced by CD4+ T helper (TH) cells at the
peak of EAM, and determined that cardiac MHC-II+ macrophages, monocytes, and monocyte-derived dendritic
cells (moDC) express the IL-3 receptor (IL-3R) at the peak of EAM, thus identifying these IL-3R+ cells as
putative IL-3 responders. Together, these data led us to propose the central hypothesis that IL-3 is essential
for driving T cell-mediated cardiac inflammation in myocarditis.
 Here, I aim to examine IL-3-mediated mechanisms that drive inflammation using two well-characterized
mouse models of myocarditis (i.e. EAM and coxsackievirus B3 (CVB3)-induced myocarditis). My specific aims
are as follows: (I) I will assess how IL-3:IL-3R signaling modulates leukocyte dynamics in myocarditis in the
heart and periphery. (II) I will define the lineage origin and characteristics of IL-3-producing T cells during
myocarditis. (III) Finally, I will also evaluate the efficacy of targeting IL-3/IL-3R signaling myocarditis
inflammation and disease outcome. Utilizing genetic knockout mice, various in vivo and in vitro analyses, flow
cytometry and cell sorting, molecular biology, histology, and imaging techniques, I aim to determine how
IL-3:IL-3R signaling shapes leukocyte function, identify subsets T cells that are drivers of IL-3-mediated cardiac
inflammation, and uncover b...

## Key facts

- **NIH application ID:** 10172970
- **Project number:** 5F31HL147364-03
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** John Edward Mindur
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $6,459
- **Award type:** 5
- **Project period:** 2019-06-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10172970

## Citation

> US National Institutes of Health, RePORTER application 10172970, Role of interleukin-3 in autoimmune and viral myocarditis (5F31HL147364-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10172970. Licensed CC0.

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