# Modulation of chemokine signaling to mitigate radiation induced inflammation -suppl Collab

> **NIH NIH U01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2024 · $100,000

## Abstract

Project Summary
Supplement title: Modulation of chemokine signaling to mitigate radiation induced Paneth cell dysfunction
The risk of large populations encountering radiation exposure is real and growing. Currently, there is a need for
strategies that mitigate gastrointestinal acute radiation syndrome. Radiation induced intestinal injury results from
loss of intestinal stem cell and dysregulation of intestinal stem cell niche. Paneth cells (PCs) located at the bottom
of small intestinal crypts are very critical member in ISC niche regulating ISC homeostasis through various
signaling pathways and growth factors. Moreover, PCs are involved in mucosal immunity by secreting
antimicrobial proteins, such as α-defensins. α-Defensins are a family of cationic peptides that form an integral
part of the innate immune system. Macrophages are important for repair and regeneration of intestinal epithelium
following irradiation. However, involvement of myeloid/ macrophages in radiation induced PC dysfunction is not
known. Radiation exposure induces recruitment of inflammatory monocytes and promotes systemic and local
inflammation. We have observed that modulation of chemokine receptor 2 signaling alters intestinal macrophage
population and mitigates GI-ARS. In this proposal by modulating CCR2/CCL2 axis with CCR2 inhibitor we will
determine the macrophage phenotype involved in regulation of PCs radiosensitivity. We will determine PCs
survival and PC derived paracrine signals in mice model of GI-ARS receiving CCR2 inhibitor. Determination of
mechanism of action will facilitate CCR2 inhibitor as a medical countermeasure against radiation under the FDA’s
Animal Rule.

## Key facts

- **NIH application ID:** 10940205
- **Project number:** 3U01AI170036-03S1
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Richard J DiPaolo
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $100,000
- **Award type:** 3
- **Project period:** 2022-07-21 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10940205

## Citation

> US National Institutes of Health, RePORTER application 10940205, Modulation of chemokine signaling to mitigate radiation induced inflammation -suppl Collab (3U01AI170036-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10940205. Licensed CC0.

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