# Bone Morphogenic Protein signaling in Th/Treg lineage specification

> **NIH NIH R03** · OLD DOMINION UNIVERSITY · 2021 · $77,500

## Abstract

Abstract
 The transforming growth factor-β (TGF-β) family cytokines regulate cell differentiation and morphogenesis, cell
proliferation and migration, epithelial-to-mesenchymal transition and metastatic dissemination. TGF-β is an
immunoregulatory cytokine well known to inhibit activation and differentiation of CD4+ effector cells and promote
suppressor functions of Foxp3+ regulatory T cells. Despite increased understanding of how TGF-β regulates T
cell functions, the immunomodulatory roles of many other members of the TGF-β cytokine family, especially
bone morphogenetic proteins (BMPs), remain largely unknown.
 We have found that Bone Morphogenic Protein Receptor 1α (BMPR1α, Alk-3) expressed by naive and
activated CD4+ T cells and Foxp3+ regulatory T (TR) cells, modulates functions effector Th and TR cells.
Abrogating BMPR1α signaling leads to generation of pro-inflammatory Th1/Th17 effector cells expressing high
levels of inflammatory cytokines, IFN-γ, IL-17 and TNF family proteins. BMPR1α-deficient CD4+ T cells do not
generate adaptive TR (aTR) cells. Inactivation of BMPR1α gene in peripheral TR cells reduced Foxp3 expression
leading to the instability of TR phenotype and accumulation of exTR cells. Jmjd3 (Kdm6b) demethylase was
identified as target of BMPR1α signaling in TR cells and epigenetic changes as a cause of lost suppressor
function. We hypothesize that BMPs and BMPR1α may represent regulatory modules shaping epigenetic
landscape and priming T cells for transcriptional regulation mediated by TGF-β.
 BMPR1α is not the only receptor binding BMPs, these cytokines may also bind activin receptors including Alk2.
To get further mechanistic insight how BMPs and TGF-β regulate functions of peripheral Th and TR cells we
propose to generate conditional knockout mice where Alk2 gene is deleted in all T cells or in TR cells. Alk2 mutant
mice will be compared to mice lacking BMPR1α gene in the respective T cell subsets. The goal of this proposal
is to produce experimental mice which could be examined to understand how Alk2 and BMPR1α cooperate to
deliver BMP and TGF-β mediated signaling to regulate CD4+ Th and TR cells.

## Key facts

- **NIH application ID:** 10194972
- **Project number:** 1R03AI159280-01
- **Recipient organization:** OLD DOMINION UNIVERSITY
- **Principal Investigator:** Piotr J. Kraj
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $77,500
- **Award type:** 1
- **Project period:** 2021-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10194972

## Citation

> US National Institutes of Health, RePORTER application 10194972, Bone Morphogenic Protein signaling in Th/Treg lineage specification (1R03AI159280-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10194972. Licensed CC0.

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