# Lung leukocytes promote alveolar epithelial regeneration after severe injury

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $635,891

## Abstract

PROJECT SUMMARY/ABSTRACT
It has become increasingly appreciated that lymphocytes within non-lymphoid tissues exhibit unique effector
programs that extend beyond their roles in anti-pathogen and anti-tumor immunity. Such non-immune functions,
including the regulation of metabolic homeostasis and tissue repair, highlight the diversity of immunological
signals that can be elaborated in a tissue-specific manner to modify physiological and developmental parameters
within a given niche. To achieve these diverse regulatory roles, tissue-localized leukocytes interact with
specialized non-lymphoid cells that define the organ’s function, triggering niche-specific effector programs in
response to perturbations within the tissue microenvironment. In support of this mechanism, a recently described
population of lung regulatory T (Treg) cells were shown to play a pronounced tissue-protective role during the
early stages of acute lung injury caused by influenza virus infection in mice. Through their production of the
epidermal growth factor receptor (EGFR) ligand, amphiregulin, these Treg cells support epithelial barrier
regeneration and preserve lung function. Although these findings uncovered an important and previously
unknown role for Treg cell–derived amphiregulin, the mechanistic details of how amphiregulin influences lung
repair remained undetermined. Preliminary studies indicate that in response to lung injury caused by other
damaging stimuli, infiltrating leukocyte populations other than regulatory T cells produce amphiregulin. Further
inspection has suggested that amphiregulin-producing leukocytes may guide alveolar epithelial regeneration by
interacting with specific lung mesenchymal and epithelial stem/progenitor cell populations that orchestrate
discrete steps of the repair process. To this end, the major goals of this proposal are to 1) characterize
interactions between amphiregulin-producing lung leukocytes and resident mesenchymal and epithelial
stem/progenitor cells, 2) identify the molecular basis of these interactions and define their relative significance
for restoring normal lung function, and 3) determine how these cellular interactions are influenced by the severity
or type of damaging stimuli. Successful completion of this project will broaden our understanding of the role of
tissue-specific immune responses in directing tissue regeneration and support the development of future
strategies that seek to stimulate these processes to treat lung disease and restore normal organ homeostasis.

## Key facts

- **NIH application ID:** 9977404
- **Project number:** 1R01HL148718-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Nicholas Arpaia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $635,891
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977404

## Citation

> US National Institutes of Health, RePORTER application 9977404, Lung leukocytes promote alveolar epithelial regeneration after severe injury (1R01HL148718-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9977404. Licensed CC0.

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