# Role of T cell-derived amphiregulin in recovery from influenza virus infection

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $197,940

## Abstract

PROJECT SUMMARY/ABSTRACT
The immune system’s role in protecting the host from influenza virus infection has been extensively studied;
however, leukocyte interactions with tissue-resident stem cells and extracellular matrix (ECM) components are
increasingly being realized as essential for mediating tissue homeostasis and recovery. While recent single-cell
RNA sequencing applications have allowed researchers to observe dynamic changes in gene expression profiles
of individual tissue cell types throughout the course of the infection, how these cells spatially network to enact
complex processes such as tissue repair remains poorly understood. As a demonstrative example of this gap in
understanding, conditional deletion of a crucial repair-related growth factor, amphiregulin (Areg), in T cells
impairs recovery after challenge with influenza virus. In light of the relatively small number of T cells among all
lung-resident amphiregulin-producing cells, their overall significance is rather striking – in addition to several
other leukocyte-derived sources of Areg, lung epithelial and mesenchymal cells have also been shown to
produce this growth factor during respiratory infections and in similar pathologic settings. Reconciling the
massive presence of Areg during repair with the non-redundant roles of Areg from distinct low-frequency cell
types necessitates further appraisal of the cell-to-cell interactions that dictate such processes. The major goals
of this project are to: (1) characterize the role of Areg’s heparin-binding domain for mediating recovery from
influenza virus infection, (2) assess the relative influence of deposited and/or cell surface–localized heparan
sulfate proteoglycans in spatially defining T cell–derived Areg signaling, and (3) determine how these tissue
processes dictate susceptibility to severe influenza outcomes. Successful completion of this proposal’s
objectives will provide a greater understanding of T cell–derived factors that mediate protection against influenza
virus and potentially impact our comprehension of immune mechanisms that contribute to severe disease.

## Key facts

- **NIH application ID:** 10105288
- **Project number:** 5R21AI149657-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Nicholas Arpaia
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,940
- **Award type:** 5
- **Project period:** 2020-02-12 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105288

## Citation

> US National Institutes of Health, RePORTER application 10105288, Role of T cell-derived amphiregulin in recovery from influenza virus infection (5R21AI149657-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10105288. Licensed CC0.

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