# Targeting Endogenous Mesenchymal Stromal Cells with Ruxolitinib to Treat Sialadenitis in Sjogren's Syndrome

> **NIH NIH R03** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $155,500

## Abstract

PROJECT SUMMARY
Sjӧgren’s disease (SjD), a common systemic autoimmune disease characterized by marked oral and ocular
sicca, has no disease modifying treatments available. Our long-term goal is to develop new effective therapies
for SjD. The objective of this application is to determine the mechanism through which ruxolitinib inhibits IFN-
induced pro-inflammatory salivary gland mesenchymal stromal cells (MSCs) and define the effects of ruxolitinib
on disease activity in SjD mouse models. The central hypothesis of the proposed studies is that IFN-
stimulated SG-MSCs, through STAT1 signaling, are pro-inflammatory and that ruxolitinib inhibits this pro-
inflammatory phenotype and ultimately reduces SG inflammation and restores saliva production in SjD mouse
models. The rationale for this hypothesis is based on our new data showing ruxolitinib abolishes IFN-induced
MSC activation and reduces MHCII upregulation in vitro through STAT1. These new data are pivotal because
they identify a possible mechanism by which the pro-inflammatory aspect of MSCs can be modified. The
central hypothesis will be tested by pursuing two specific aims: (1) Determine the effect of ruxolitinib on SG-
MSC immunobiology in vitro and (2) define the effects of ruxolitinib on SG-MSC and whole gland phenotype
and function in vivo. Under the first aim, SG-MSCs from SjD and control patients will be treated with IFN ±
ruxolitinib and phenotype and functional differences will be examined in vitro. Chromatin immunoprecipitation-
sequencing will be performed to determine the mechanism by which ruxolitinib imparts change in the
immunomodulatory profile of SG-MSCs. For the second aim, two SjD mouse models will be treated with
ruxolitinib or vehicle. SG-MSCs will be isolated and interrogated from each treatment group. Next, a global
salivary gland and systemic evaluation will be performed. The research proposed in this application is
innovative because traditionally the anti-inflammatory profile of IFN-treated MSCs has been the focus of
research. This proposal focuses on how IFN creates a pro-inflammatory MSC phenotype that can be inhibited
with ruxolitinib. Furthermore, SjD research has focused on JAK1 inhibition and we propose the use of a JAK1
& 2 inhibitor to treat SjD. The proposed research is significant because ruxolitinib holds promise as a feasible
modality to promote anti-inflammatory resident MSCs and for systemic SjD treatment. Should this pilot study
determine the mechanism by which ruxolitinib creates anti-inflammatory MSCs or that ruxolitinib improves SjD
in mice, these finding will be harnessed toward novel MSC-based or systemic treatment of SjD.

## Key facts

- **NIH application ID:** 10524424
- **Project number:** 1R03DE031340-01A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Sara Mccoy
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $155,500
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10524424

## Citation

> US National Institutes of Health, RePORTER application 10524424, Targeting Endogenous Mesenchymal Stromal Cells with Ruxolitinib to Treat Sialadenitis in Sjogren's Syndrome (1R03DE031340-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10524424. Licensed CC0.

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