# Neuregulin signaling in myeloid cells

> **NIH NIH R01** · MAINEHEALTH · 2024 · $581,578

## Abstract

Our new preliminary data indicate that ErbB3 signaling is essential for the integration of early inflammatory
response with adaptive immunosuppression, thus preventing the activation of cardiac lymphocytes and
protecting the heart against secondary immune cell-mediated tissue damage. We found that ErbB3
upregulates the expression of PD-L1 on myeloid cells in response to their stimulation with inflammatory factors.
Myocardial tissue lymphocytes express high levels of PD-1 that inhibit the activation of T cells upon binding to
PD-L1 on myeloid cells. Reduced level of PD-L1 expression in mice with disrupted ErbB3 signaling is
associated with activation of cytotoxic lymphocytes and myocardial dysfunction in a mouse model of LPS-
driven inflammation. We also found that ErbB3 promotes up-regulation of PD-L1 after ischemia-reperfusion
(I/R) cardiac injury. To better understand the role of ErbB3 in the regulation of the PD-L1/ PD-1 axis and
myocardial protection, we generated novel mouse models with ablation and overexpression of ErbB in myeloid
cells and subsets of myeloid cells, including macrophages, dendritic cells, and Ly6Clow monocytes. In specific
aim 1, we will determine the role of ErbB3 in the regulation of the myocardial PD-L1/PD-1 axis and
immunosuppression during the acute inflammatory response using loss-of-function and gain-of-function mouse
models. In specific aim 2, we will test the hypothesis that ErbB3 downstream signaling promotes synthesis and
prevents degradation of PD-L1 in myeloid cells. In specific aim 3, we will determine the role of lymphocyte
activation and Ly6Clow monocytes in the promotion of fibrosis in remote myocardial areas in mice with disrupted
ErbB3 signaling in myeloid cells.

## Key facts

- **NIH application ID:** 10978859
- **Project number:** 2R01HL136560-05A1
- **Recipient organization:** MAINEHEALTH
- **Principal Investigator:** Sergey Ryzhov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $581,578
- **Award type:** 2
- **Project period:** 2017-07-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978859

## Citation

> US National Institutes of Health, RePORTER application 10978859, Neuregulin signaling in myeloid cells (2R01HL136560-05A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10978859. Licensed CC0.

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