# Salivary gland response to innate immune mediators dictates Sjogren's syndrome development

> **NIH NIH R21** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2021 · $262,200

## Abstract

Project Summary
 Sjögren's syndrome (SS) is a systemic autoimmune disorder affecting multiple organ
systems. A dysregulated immune response targeting the exocrine salivary and lacrimal glands
reduces fluid secretion, which manifests into the dry mouth and dry eye symptoms of SS. Recent
evidence in the literature suggests that innate immune activation is a prominent etiologic factor.
Nevertheless, how a systemic or localized innate immune response transitions into an adaptive
autoimmune response and targets the exocrine glands remains unclear. This issue is also highly
relevant in the context of the ongoing COVID-19 pandemic. In genetically susceptible
individuals, the systemic cytokine storm elicited by the SARS-CoV-2 infection and the salivary
gland tropism of this virus may heighten the risk for developing SS or worsening its severity.
 The presence of lymphocytic infiltrates in exocrine glands is a significant feature of SS.
These infiltrates are predominantly peri-ductal, suggesting that ductal cells are involved in
initiating inflammatory cell infiltration into the salivary glands. By using the innovative
collaborative cross mice and poly(I:C) as a surrogate for viral infection, this proposal will
investigate how the genetic regulation of innate immunity in salivary gland epithelial cells
(SGEC) influences SS development. We will test the overall hypothesis that in genetically
susceptible individuals, the SGEC response to innate immune stimuli dictates lymphocytic
infiltration into the salivary glands and SS development. To test this hypothesis, in Aim 1, we
will investigate whether the hierarchy of systemic IFN responses in collaborative cross mice
influences lymphocytic infiltration within the salivary glands. In Aim 2, we will investigate
whether the genetic makeup of SGECs dictates the magnitude of their response to innate
immune mediators.
 The successful completion of this proposal will help decipher the influence of a
differential gradient of innate immune responsiveness in SS pathogenesis. Further, SS
development in any of the collaborative cross mice used in this proposal will provide the SS
research community a more patient-relevant model system to investigate gene-environment
interaction(s) in the disease.

## Key facts

- **NIH application ID:** 10317601
- **Project number:** 1R21DE031166-01
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** Umesh S Deshmukh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $262,200
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317601

## Citation

> US National Institutes of Health, RePORTER application 10317601, Salivary gland response to innate immune mediators dictates Sjogren's syndrome development (1R21DE031166-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10317601. Licensed CC0.

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