# Genetic determinants of myeloid cell homeostasis and tissue distribution

> **NIH NIH R21** · ROCKEFELLER UNIVERSITY · 2021 · $181,196

## Abstract

Project Summary
Myeloid cells are relatively short-lived, and must be continuously replaced to maintain normal
homeostasis. Recent findings showed that variation in immune cell homeostasis exists between
individuals. Although non-heritable factors such as age, sex and latent infections can affect
variation in immune cell frequencies, data from twin studies suggest a high level of genetic
determinism. The object of this proposal is to appreciate the role that host polymorphisms play in
steady-state homeostasis using the Collaborative Cross (CC) and Diversity Outbred (DO) animal
models that reflect the genetic diversity of an outbred population such as humans. These strains
are an ideal resource for high-resolution genetic mapping and will therefore provide a powerful
experimental system to test the hypothesis that variation in myeloid cell homeostasis is genetically
regulated, and to map the source of the diversity. We first propose to conduct a comprehensive
screen of CC and DO strains for systemic and tissue levels of myeloid cells to estimate the
diversity resulting from natural genetic variation (Aim 1). Using high-resolution QTL mapping in
the DO, we will identify genes that underlie variation in myeloid cell homeostasis and tissue
distribution; we will use CC strains for in vivo experimental validation of these genes and
mechanistic studies (Aim 2). Altogether exploratory experiments proposed in this project
represents a major effort to elucidate the association between genotype and immune cell numbers
and will provide a rich resource for interrogating the homeostatic mechanisms governing the
balance of immune cells in tissues.
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## Key facts

- **NIH application ID:** 10227989
- **Project number:** 5R21AI145369-02
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Gaelle Breton
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $181,196
- **Award type:** 5
- **Project period:** 2020-08-03 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227989

## Citation

> US National Institutes of Health, RePORTER application 10227989, Genetic determinants of myeloid cell homeostasis and tissue distribution (5R21AI145369-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10227989. Licensed CC0.

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