# Stromal cells in immunity to infection

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $560,649

## Abstract

Project Summary
The objective of our work is to decipher how stromal cells interact with immune cells to alter tissue biology to
support resistance to an intestinal infection. Our work will use mice infected with the intestinal helminth
parasite Heligmosomoides polygyrus bakeri (Hp), which is a recognized inducer of type 2 immunity. In this
system, mice are resistant to reinfection following curative treatment of primary infection, and resistance is Th2
cell-dependent. We recently reported that during Hp infection mesenteric adipose tissue (mAT) becomes
populated by long-lived Th2RM cells which make Amphiregulin and TGFβ1 in addition to the signature Th2
cytokines IL-4, IL-5 and IL-13, and that deletion of the Amphiregulin receptor on stromal cells is associated with
increased susceptibility to Hp. Further, stromal cells within mAT, and especially a subset of stromal cells with
multipotent potential (multipotent progenitor cells, MPC) to differentiate into fibroblasts or adipocytes, become
activated and makes the alarmins IL-33 and TSLP that are able to promote Th2 RM cell activation. We have
localized both Th2RM cells and MPC to interstitial spaces in mAT. We propose that mAT interacts with the
intestine to participate in the protective response against Hp. This involves the production of alarmins to
support Th2RM cell activity, and to produce extracellular matrix (ECM), which we postulate is important for
trapping invading parasites in granulomas, and supporting soft tissue integrity and repair during infection.
Based on our published findings and new preliminary data, we hypothesize that Th2RM cells and stromal cells
work as a team to mutually facilitate each other’s activation and exert host protective effects during Hp
infection. On the basis of our recently published findings and new preliminary data on innate training in MPC,
and lipid metabolism and motility of Th2RM cells, we have developed two Specific Aims: 1, To understand the
role of MPC in shaping host resistance to Hp; and 2, To determine the function, antigen specificity, and cell-
intrinsic metabolic and migratory features of mAT-resident Th2 cells. To address these Aims we will use RNA
seq, ATACseq, flow cytometry, parasitological techniques, advanced imaging of cell movement ex-vivo,
measurements of tissue stiffness, ex-vivo studies of the functional properties of Th2RM cells and stromal cells,
and in vivo loss of function models to probe the roles of Amphiregulin, TGFβ, IL-33 and TSLP. Our work has
the potential to reveal novel features of stromal cell biology that are integral to underlying effector mechanisms
of resistance and immunity to intestinal pathogens, and to highlight potential points of intervention for
manipulating stromal cell biology as it relates to type 2 immunity in health and disease. Our findings may have
relevance to understanding human conditions such as atopy/allergy, impaired wound healing, fibrosis and
cancer, in which dysregulated stromal cell biology...

## Key facts

- **NIH application ID:** 10849892
- **Project number:** 5R01AI177287-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** EDWARD J. PEARCE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $560,649
- **Award type:** 5
- **Project period:** 2023-05-26 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10849892

## Citation

> US National Institutes of Health, RePORTER application 10849892, Stromal cells in immunity to infection (5R01AI177287-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10849892. Licensed CC0.

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