# Cytokines driving T cell dysregulation in lacrimal gland autoimmunity

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $501,347

## Abstract

PROJECT SUMMARY
Sjögren syndrome is a chronic autoimmune disease characterized by immune-mediated
destruction of lacrimal and salivary glands leading to vision-threatening dry eye disease,
profound dry mouth, and overall decreased quality of life. The immunopathogenesis of Sjögren
syndrome is poorly understood, and treatments fail to halt the autoimmune destruction of the
targeted glands. There is a critical need to identify mechanisms of disease initiation to overcome
barriers to designing effective therapies. Disease initiation precedes clinical manifestations by
years (even decades) precluding such studies in humans. Nonobese diabetic (NOD) mice
develop spontaneous autoimmunity of lacrimal and salivary glands with several features
resembling Sjögren syndrome in humans including the central role of T cells in mediating the
autoimmune attack on these glands. We have recently discovered that lacrimal gland
autoimmunity in NOD mice requires interleukin 27 (IL27) and type I interferons (IFN). These
cytokines are complex with both immunostimulatory and immunomodulatory effects depending
on the context. Thus, directly targeting IL27 or type I IFN may not be appropriate in the
treatment of Sjögren syndrome. The long-term goal of our research is to identify new
therapeutic targets for Sjögren syndrome. Our objectives in this proposal are to identify
mechanisms by which IL27 and type I IFN drive lacrimal gland autoimmunity in the NOD mouse
model of Sjögren syndrome. Our central hypothesis is that innate immune signals (eg, type I
IFN) promote lacrimal gland antigen presenting cells to produce IL27, which drives pathogenic
effector T cells to target lacrimal glands. Our specific aims to test this hypothesis are: (1) Identify
the cellular targets of IL27 and downstream effects on effector T cells required for lacrimal gland
autoimmunity; (2) Define the upstream triggers of IL27 including the role of type I IFN in driving
male-specific lacrimal gland disease. We will use the NOD mouse-based spontaneous disease
model, genetically edited NOD strains, our adoptive transfer model, bone marrow chimeras, and
in vitro cultures to pursue these studies. The significant positive impact of completing these
studies includes identifying mechanisms by which human disease-relevant cytokines drive T cell
dysregulation in lacrimal gland autoimmunity, which will lead to novel therapies to halt the
autoimmune attack. Given the roles of IL27 and type I IFN in other autoimmune diseases, these
findings may lead to therapies for other autoimmune diseases as well.

## Key facts

- **NIH application ID:** 9891066
- **Project number:** 5R01EY027731-03
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Scott Matthew Lieberman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $501,347
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891066

## Citation

> US National Institutes of Health, RePORTER application 9891066, Cytokines driving T cell dysregulation in lacrimal gland autoimmunity (5R01EY027731-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9891066. Licensed CC0.

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