# Ocular Immune Regulation by Mesenchymal Stem Cells

> **NIH NIH R01** · SCHEPENS EYE RESEARCH INSTITUTE · 2021 · $124,999

## Abstract

Summary of Parent R01 Award (EY024602)
Renowned for promoting tissue regeneration and immune quiescence, studies have demonstrated the
therapeutic potential of MSCs in human disease. Nevertheless, fundamental questions remain unanswered
regarding their immunomodulatory mechanisms. This proposal employs a well-characterized transplant
model of the murine cornea to systematically investigate how MSCs directly interact with T cells to suppress
alloimmunity. Over recent years the work of several laboratories, including our own, has made substantial
progress in understanding how MSCs regulate ocular inflammation. With respect to corneal transplantation,
we and others have shown that exogenous administration of MSCs suppresses alloimmunity and promotes
graft survival. Reports from our lab provide evidence that MSCs: (i) specifically home to the ocular surface
following corneal transplantation, where they act to (ii) limit antigen-presenting cell (APC) maturation, and
(iii) decrease graft-destroying IFNγ + T helper-1 (Th1) cell responses. Moreover, our preliminary data and
reports from other groups indicate that administration of MSCs following transplantation induces Foxp3+
regulatory T cells (Tregs). Despite these observations, the exact mechanisms by which MSCs suppress Th1
generation and induce Tregs are not known. Our preliminary investigations indicate that, in addition to
indirect modulation via APCs, MSCs exert a direct immunomodulatory effect on alloreactive T cells. We
define 3 specific aims to answer the following questions: Aim 1: What are the mechanisms by which MSCs
inhibit generation of alloreactive Th1 cells? Aim 2: What are the mechanisms by which MSCs inhibit effector
function of alloreactive Th1 cells? And finally Aim 3: How do MSCs promote the generation of tolerance-
inducing Tregs? Our preliminary data implicate specific soluble and surface-bound immunoregulatory
molecules. Based on these data, we propose 3 hypotheses: (1) MSCs negatively regulate early T cell
activation via the surface-bound molecule ALCAM, resulting in decreased generation of Th1 cells; (2) MSC-
secreted IL11 suppresses Th1 function by antagonizing IFNγ and Tbet expression; and (3) MSCs skew the
differentiation of naïve T cells toward Foxp3+ Tregs via CD80/CTLA-4 interaction. Principal objective of this
project is to define the molecular mechanism by which MSCs interact with T cells to regulate alloimmunity.
In this proposed supplement, we plan to apply our understanding of the immunomodulatory and
cytoprotective functions of MSCs to promote the survival of ocular cells following nitrogen mustard
exposure. In the parent grant, we investigate how MSCs suppress ocular inflammation in a model of
adaptive immunity. Here, we will investigate whether MSCs or their secreted immunoregulatory and
growth factors provide similar protective functions following vesicant-induced injury.

## Key facts

- **NIH application ID:** 10219739
- **Project number:** 3R01EY024602-06S1
- **Recipient organization:** SCHEPENS EYE RESEARCH INSTITUTE
- **Principal Investigator:** Sunil K Chauhan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $124,999
- **Award type:** 3
- **Project period:** 2015-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219739

## Citation

> US National Institutes of Health, RePORTER application 10219739, Ocular Immune Regulation by Mesenchymal Stem Cells (3R01EY024602-06S1). Retrieved via AI Analytics 2026-08-01 from https://api.ai-analytics.org/grant/nih/10219739. Licensed CC0.

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