# Role of macrophage polarization in multi-organ fibrosis of chronic GVHD

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $547,124

## Abstract

Project Summary/Abstract
Chronic graft versus host disease (cGVHD) represents the leading cause of non-relapse mortality and
morbidity after allogeneic hematopoietic stem cell transplantation (HCT). It is typically clinically manifested as
an autoimmune-like syndrome and systemic fibrosis. Recent studies have suggested that macrophages with
an anti-inflammatory M2-phenotype are capable of promoting fibrosis in cGVHD. However, it remains largely
undefined what drives the polarization of M2 macrophages at sites of cGVHD and how M2 macrophages
promote GVHD-related fibrotic changes. The objective of this application is to understand the role of hedgehog
(Hh) signaling in the polarization of M2 macrophages and systemic fibrosis. Specifically, we will test the
hypothesis that the Hh signaling pathway is critical for M2 macrophage polarization in cGVHD target organs,
which in turn promotes fibrosis through the production of fibrogenic factors. We will employ mouse models and
human tissues to pursue four specific aims that will allow us to define the role of Hh signaling and the source of
sonic hedgehog (SHH) in promoting pro-fibrotic macrophages in cGVHD; we will delineate molecular
mechanisms and factors mediated by macrophages that lead to an ongoing pro-fibrotic state in GVHD, and
end-organ fibrosis in cGVHD. The long-term objective of this project is to define the role of Hh signaling in
cGVHD by providing a mechanistic understanding of its effects on macrophage polarization within GVHD
target organs and its contributions to immune cell dysregulations and tissue fibrosis. Our work may lead to the
development of novel therapeutic strategies for treating systemic fibrosis in cGVHD.

## Key facts

- **NIH application ID:** 10072171
- **Project number:** 1R01HL151195-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Xiaopei Huang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $547,124
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072171

## Citation

> US National Institutes of Health, RePORTER application 10072171, Role of macrophage polarization in multi-organ fibrosis of chronic GVHD (1R01HL151195-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10072171. Licensed CC0.

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