# Novel lung resident interstitial macrophage subset with distinct localization and polarization

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $572,342

## Abstract

ABSTRACT
The importance of tissue resident macrophages for pathogen clearance and homeostasis is beginning to
emerge. However, our understanding of the multifaceted roles these macrophages play in mucosal tissues such
as the lung remains incomplete. The lung is a very complex organ with specialized structures to allow for
adequate gas exchange. The pulmonary microenvironment is unique and has a direct and important influence
on the resident immune cells, especially macrophage populations. Currently, it is well established that lung
harbors two distinct populations of macrophages known as alveolar macrophages (AMs) and interstitial
macrophages (IMs). One of the most important function of pulmonary macrophages is to regulate inflammatory
pathways during infection and allow for the resolution inflammation after the pathogen is cleared. The precise
mechanisms that macrophage populations utilize to accomplish these critical functions in vivo are not well
understood. For example, Macrophages play a critical role in regulating pathogen induced inflammation during
a respiratory infection such as with influenza. Influenza infection causes worldwide yearly epidemics resulting
in thousands of deaths and hospitalizations. Clinical complications are caused by tissue damage due to
excessive viral-induced immune responses. Thus, there is a critical need to understand the cellular and
molecular mechanisms that cause infection-induced inflammation and pathology in vivo in order to develop new
therapeutic strategies to alleviate damaging inflammation during infection. Here we report a previously
uncharacterized subset of pulmonary macrophages that are exclusively localized around the large bronchiole
airways. We have termed these cells as large airway associated interstitial macrophages (LAAMs). Our
preliminary data show that the transcriptional gene signature of the LAAMs is remarkably unique when compared
to AMs with high expression of regulatory genes and thus, we believe that these cells play an important role in
regulating influenza-induced inflammation in vivo. Furthermore, the unique and exclusive localization of LAAMs
to the large airways suggests that these macrophages may serve a ‘gatekeeper’ function within the complex
structure of the lung. Thus, we hypothesize that LAAMs define a novel population of macrophages completely
distinct from other pulmonary macrophages such as AMs, and their unique positioning, remarkable gene
expression profile, and the notable reaction to influenza infection make them critically important for regulating
immune and tissue homeostasis and pathogen-induced inflammation. We propose the following aims:
Aim1: To determine the ontogeny, maintenance and cellular heterogeneity of LAAMs; Aim2: To determine the
physiological significance of LAAMs and AMs following infection; Aim3: To determine the mechanisms, that
allow LAAMs to regulate immune/tissue homeostasis in steady-state conditions or during respiratory infection.

## Key facts

- **NIH application ID:** 10320372
- **Project number:** 5R01AI143861-04
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Kamal Mohan Khanna
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $572,342
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320372

## Citation

> US National Institutes of Health, RePORTER application 10320372, Novel lung resident interstitial macrophage subset with distinct localization and polarization (5R01AI143861-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10320372. Licensed CC0.

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