# Role of bone marrow Tregs in maintaining stromal cell function

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $371,250

## Abstract

PROJECT SUMMARY / ABSTRACT
Regulatory T cells (Tregs) are known for not only their ability to regulate immune response, but also for their
heterogeneity and non-canonical functions in tissue maintenance. As recently suggested tissue-specific Tregs
have specialized functions to maintain those tissues in which they exist, and in adipose tissue, lung, and skin
function to support local tissue stem cells. Accumulating evidence suggests that the stromal microenvironment
regulates immune response; we propose that the reverse is also true, specifically through marrow Treg and
stromal cell interactions. Interestingly, Tregs represent approximately one-third of all CD4+ T lineage cells in
the marrow, a portion that is significantly higher than other hematopoietic tissues; however, the function of
tissue resident Tregs in the maintenance of the bone microenvironment and underlying molecular signature
remain unclear. Our focus is to uncover the signaling pathways that marrow Treg use to maintain
mesenchymal stromal cell's differentiation and hematopoietic stem cells support. We have found that depletion
of Tregs alters the bone marrow microenvironment, and more specifically increases cycling and alters
differentiation of mesenchymal stromal cells. Based on our preliminary data, we propose that marrow Tregs
are a unique subpopulation of immune cells with preferential bias to circulate back to the bone marrow and this
is supported by their unique chemokine and cytokine receptor profile. Our research identifies Tregs as the
major source of interleukin-10 (IL-10) in the marrow; and support a role for Treg-secreted IL-10 as a main
factor that supports stromal cell functions. In ongoing studies, we are trying to define the IL-10 specific
mechanisms of stromal cell maintenance. We propose to define how IL-10 signaling pathways in stromal cells
support their maintenance (Aim 1). We will characterize the function and transcriptional characteristics of
marrow stromal cells using stromal cell fate-mapping mouse models following IL-10 and Treg perturbation to
define the molecular drivers for maintenance during hematopoietic stem cell transplants (Aim 2). We expect
that these experiments will define new regulatory networks by establishing bi-directional communication
between highly specialized tissue-resident lymphocytes and marrow stromal cells. These results will provide
the basis for studies to understand how infections, transplantation, or disease may impact these interactions.
We will exploit these interactions to impede pre-malignant clones by altering the marrow microenvironment
(Aim 3). Moving forward, these findings could lead to therapeutic targets for improved bone marrow
transplantation or changing outcomes in hematopoietic disease.

## Key facts

- **NIH application ID:** 10052818
- **Project number:** 1R01HL150078-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Robert S Welner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,250
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052818

## Citation

> US National Institutes of Health, RePORTER application 10052818, Role of bone marrow Tregs in maintaining stromal cell function (1R01HL150078-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10052818. Licensed CC0.

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