# T-Cell-Mediated Inflammatory Response in Neonatal Heart Regeneration

> **NIH NIH P01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $311,601

## Abstract

Project Summary/Abstract
The neonatal mouse heart possesses a remarkable ability to regenerate following injury and this cardiac
regeneration is closely accompanied by robust activation of the immune system. Studies in the last decade have
focused on the role of innate immunity during neonatal heart regeneration, and have established the necessary
roles for macrophages in the repair and regeneration processes following myocardial infarction (MI). However,
macrophages alone are not sufficient to drive neonatal regeneration, as neonatal mice lacking adaptive immunity
but retaining innate immunity cannot regenerate. This result strongly suggests that other immune cells such as
those involved in adaptive immunity also play a role in neonatal heart regeneration. In this project, we aim to
explore the role of adaptive immunity, in particular the CD4+ T helper 2 (Th2) cell-mediated inflammatory
response as a bridge between adaptive and innate immune signaling pathways that mediate neonatal
cardiomyocyte (CM) proliferation in response to injury. Our preliminary results revealed that the Th2 cell secreted
cytokine interleukin 4 (IL-4) is strongly upregulated in neonatal day 1 mouse hearts after MI and can promote
CM proliferation. Its receptor IL-4ra is highly expressed in the proliferating CM population. We hypothesize that
the Th2 cell-mediated IL-4 signaling promotes CM proliferation and macrophage transformation, as well as
generating the cardiotropic factor CCL24 as a critical cytokine pathway in neonatal heart regeneration.
Understanding how immune cells participate in neonatal heart regeneration will enlighten the development of
potential therapeutics to promote adult heart repair and regeneration in humans.

## Key facts

- **NIH application ID:** 10821377
- **Project number:** 5P01HL160488-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** ERIC N Olson
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $311,601
- **Award type:** 5
- **Project period:** 2023-04-05 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821377

## Citation

> US National Institutes of Health, RePORTER application 10821377, T-Cell-Mediated Inflammatory Response in Neonatal Heart Regeneration (5P01HL160488-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10821377. Licensed CC0.

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