# Functions of ductal- and stromal-associated macrophages in the mammary gland

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2024 · $479,517

## Abstract

PROJECT SUMMARY
 Tissue resident macrophage function has emerged as a critical component controlling the balance
between organ health and disease. In the mammary gland, macrophages are closely associated with the
ductal epithelium and have important phagocytotic roles to maintain tissue homeostasis. Recent studies from
our laboratory and others revealed distinct ductal- and stromal-associated tissue resident macrophages that
contribute to maintaining the developing ductal structures. However, the important macrophage-derived factors
that regulate mammary gland development and the mechanisms by which these distinct macrophage
populations maintain the homeostatic state are poorly understood. The overall goal of these studies is to define
the functions and mechanisms by which tissue resident macrophages contribute to ductal remodeling
throughout distinct stages of mammary gland development. Our preliminary studies identify transcriptional
profiles of distinct macrophage populations in the mammary glands of adult mice. We show that two key
factors, Cebpb and Gas6, are highly expressed in ductal- and stromal-associated macrophages, respectively,
providing potential mechanisms for macrophage function in mammary gland development. Genetic ablation of
these factors results in alterations in the mammary gland during key developmental windows. We hypothesize
that C/EBPb and Gas6 are crucial effector molecules that drive distinct functions of ductal and stromal
macrophages, respectively, during key stages of mammary gland development. In aim 1, we will characterize
macrophage heterogeneity throughout postnatal development and determine the functions of distinct
macrophage populations in mammary gland development. In Aim 2, the mechanisms of how C/EBPb-induced
factors in ductal macrophages alter stem cell expansion will be determined. In Aim 3, Gas6-dependent
mechanisms of collagen homeostasis by stromal macrophages will be determined. Impact: Throughout
mammary gland development, there are critical windows that are highly susceptible to mutagenic events.
Although macrophages have been well-studied during tumor progression and metastasis, the mechanisms
driving tissue resident macrophage function during these key stages of development are not known.
Understanding these mechanisms will advance our understanding of how tissue resident macrophages impact
mammary tissue homeostasis, and provide insight into how disrupted tissue homeostasis leads to disease,
such as tumorigenesis.

## Key facts

- **NIH application ID:** 10885118
- **Project number:** 5R01HD106929-03
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Heather L Machado
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $479,517
- **Award type:** 5
- **Project period:** 2022-09-07 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885118

## Citation

> US National Institutes of Health, RePORTER application 10885118, Functions of ductal- and stromal-associated macrophages in the mammary gland (5R01HD106929-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10885118. Licensed CC0.

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