# Regulation of tissue resident macrophage development by IL-7R signaling

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, MERCED · 2020 · $373,231

## Abstract

The recent discovery that adult hematopoietic (blood) stem cells (HSCs) do not produce all immune cells
despite sustaining blood production across the lifespan has fundamentally challenged our understanding of
both immune development and function. Adoptive transfer studies and fate mapping experiments have
demonstrated that tissue-resident macrophages are only specified during fetal development and cannot be
generated or regenerated in adulthood. As compared to their adult HSC-derived counterparts, fetal-derived
tissue resident macrophages reside and self-renew within their resident tissues, where they perform distinct
homeostatic and immune surveillance functions. The discovery of a fetal origin of tissue-resident macrophages
has raised many new questions about their specification, persistence across the lifespan, and distinct function.
The long-term objective of this proposal is to define the developmental mechanisms underlying the unique
functional capacity of tissue resident macrophages across the lifespan in order to illuminate their distinct role in
both adult tissue homeostasis and disease. Recent work in our lab has identified interleukin-7 receptor (IL-7R)
signaling as a novel mechanism regulating the establishment of tissue resident macrophages during fetal
development. IL-7R signaling is restricted to regulation of the lymphoid lineage in adult hematopoiesis. The
reliance of fetal myeloid specification on IL-7R signaling suggests that fetal hematopoiesis exploits alternate
differentiation pathways in order to confer distinct characteristics on fetal-derived macrophages. In this
proposal, we will capitalize on the discovery of this new regulatory mechanism to dig deeper into how these
distinct immune cells are specified from fetal precursors during development. In Aim 1, we will use genetic
approaches to determine the requirement for IL7R signaling during fetal myeloid specification. We will
specifically delete the receptor sub-chain IL7raain a range of progenitors and mature cells at different stages of
development to define how IL7rα regulates myeloid specification during fetal development. In Aim 2, we will
define for the first time how IL-7R signaling occurs in myeloid cells - including downstream signal transducers
and transcriptional targets- and the specific developmental processes that are regulated by IL-7R signaling
during fetal macrophage establishment. In Aim 3, we will establish the function of IL-7 as a fetal myeloid niche
factor and define both the requirement for IL-7 and which cell subsets are responsible for producing IL-7 within
resident tissues to support macrophage development. Together, work from the proposed studies will illuminate
how alternative differentiation pathways during fetal hematopoiesis impart distinct functional characteristics on
fetal-derived tissue resident macrophages, and thereby illuminate the role of specific ontogenetic subsets of
macrophages in normal tissue and disease processes.

## Key facts

- **NIH application ID:** 9883828
- **Project number:** 5R01HL147081-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, MERCED
- **Principal Investigator:** Anna E Beaudin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $373,231
- **Award type:** 5
- **Project period:** 2019-03-01 → 2020-03-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9883828

## Citation

> US National Institutes of Health, RePORTER application 9883828, Regulation of tissue resident macrophage development by IL-7R signaling (5R01HL147081-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9883828. Licensed CC0.

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