# Differential roles for type I interferon and inflammatory pathways in autoimmune diabetes

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $592,406

## Abstract

Project Abstract
! Despite decades of intensive research, type 1 diabetes (T1D), which is characterized by autoimmune
destruction of the insulin-producing beta cells of the pancreas, still cannot be prevented. Understanding the
innate immunologic mechanisms for the development of T1D is crucial for developing preventive strategies.
Dissecting the interactions between environmental stimuli such as viral infection, immune responses, and the
development of insulitis (a key pathologic feature of T1D) in humans is extremely challenging. By temporally
defining such interactions in the rat model of autoimmune diabetes, we believe we can develop specific
interventions to target the human disease process.
 We have found that the type I interferon (IFN) receptor (IFNAR), a key component of the innate immune
response to viral infection, is critically involved in development of virus-induced autoimmune diabetes in
weanling LEW.1WR1 rats. We will further define the role of type I IFN in the development of diabetes by
comparing immune cell recruitment between WT and IFNAR-/- rats and examining transcriptional profiles at the
single cell level. We will also determine if intrinsic IFN signaling in islets, including beta cells, contributes to the
development of T1D by performing islet transplants between WT and IFNAR-/- rats. Inflammatory pathways
also participate in the pathogenesis of autoimmune diabetes. We will determine if blockade of the interleukin-1
(IL-1) receptor will prevent type I IFN-independent diabetes. We will delineate mechanisms by which the anti-
inflammatory drug salicylate prevents diabetes. We plan to create a knockout rat using a CRISPR-Cas9 gene
editing strategy to examine the inflammatory pathway-mediated contribution to the development of
autoimmune diabetes.
 Through the proposed studies, we will gain a fundamental understanding of immunologic responses
that lead to autoimmune diabetes. Notably, we will define both temporal aspects as well as key cell populations
involved in innate immune responses. Results from these experiments will reveal specific innate immune
pathways that participate in the development of insulitis and autoimmune diabetes and are essential for
developing preventive strategies for individuals who are at greatest risk for T1D.

## Key facts

- **NIH application ID:** 10189495
- **Project number:** 5R01AI139095-04
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Jennifer P Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $592,406
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10189495

## Citation

> US National Institutes of Health, RePORTER application 10189495, Differential roles for type I interferon and inflammatory pathways in autoimmune diabetes (5R01AI139095-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10189495. Licensed CC0.

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