# Understanding Immune-Stromal Interactions in Tissue Homeostasis and Inflammation

> **NIH NIH R35** · BOSTON CHILDREN'S HOSPITAL · 2024 · $442,500

## Abstract

SUMMARY
In tissues, immune cells are well-organized spatially and perform specific functions to dictate tissue homeostasis
and inflammation. Yet, it is rarely understood how the organization and functions of immune cells are regulated
by their surrounding tissue stroma. The overall vision of the lab is to elucidate the impacts and mechanisms of
the interactions between immune and non-immune cell types, in order to understand general principles of how
immune functions are regulated within tissues. This may ultimately lead us to program immune responses to
restore tissue homeostasis from disease. The lab has discovered that macrophages and fibroblasts, two cell
types that are commonly present in mammalian tissues, self-assemble into a tissue-like system that maintains a
stable and robust population composition. These homeostatic features rely on paracrine communication of
growth factors and direct contact between these cells. This macrophage-fibroblast system provides a unique,
accessible and modular platform to discover immune functions in the cellular context of stromal cells and to
dissect the underlying mechanisms. Our published and preliminary data formulate the overall hypothesis of the
lab: distinct cellular responses emerge from the interactions between macrophages and fibroblasts.
The goal of the lab in the next five years is to identify the cellular and molecular bases of the interactions between
macrophages and fibroblasts and to characterize how these interactions regulate immune responses during
tissue homeostasis or inflammation. We aim to elucidate general principles that regulate functions and
organization of immune cells in tissues, by developing new methods to study their interactions and interactive
partners, discovering interaction receptors to perturb them, and defining cellular functions dependent on such
interactions. To reach this goal, 3 directions will be pursued in my lab: 1) develop fucosyl-labeling, a new cell-
based chemical genetic approach, to identify cell-cell interactions, 2) identify molecules responsible for the
physical association between macrophages and fibroblasts, leveraging candidate-based genetic approaches, 3)
determine how the interactions between macrophages and fibroblasts impact their cellular responses under
inflammatory conditions using transcriptome profiling, imaging and immunological assays. Research proposed
in this application is innovative because it presents a comprehensive strategy to directly tackle the mechanistic
nature of immune-stromal interactions, combined with exploration of a new research paradigm and the
development of cutting-edge technologies that will have a fundamental impact in basic cell biology and
immunology.
The proposed research is significant because it will identify the cellular mechanisms that regulate
immune functions critical for maintaining tissue homeostasis and regulating inflammatory responses. My lab will
advance our knowledge of inter-cellular processes that m...

## Key facts

- **NIH application ID:** 10891600
- **Project number:** 5R35GM151000-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** XU ZHOU
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $442,500
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891600

## Citation

> US National Institutes of Health, RePORTER application 10891600, Understanding Immune-Stromal Interactions in Tissue Homeostasis and Inflammation (5R35GM151000-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10891600. Licensed CC0.

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