# The role of IL-27 signaling in the accumulation and sustained effector function of autoreactive CD8 T cells in type 1 diabetes

> **NIH NIH F31** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $37,079

## Abstract

Project Summary
Type I diabetes (T1D) is a chronic autoimmune disease in which T cells destroy insulin-producing pancreatic β
cells. T1D results from a complex interaction between genetic predisposition and environmental factors.
Completely defining the genetic and environmental factors that contribute to disease susceptibility is crucial to
finding successful therapies in the treatment and prevention of T1D. Human IL27 (encodes a subunit of the
cytokine interleukin (IL)-27) is a T1D candidate gene located in a susceptibility region on chromosome 16. The
function of IL-27 in T1D pathogenesis is unknown. The long-term goal of this project is to define the role of
IL-27 in the progression of T1D. CD8 T cells are the main effectors mediating β cell damage but they require
help from CD4 T cells. Previous studies with both human and mouse have shown that IL-27 signaling can
regulate T cell function. Our lab has generated non-obese diabetic (NOD) mice deficient in IL-27 or IL-27
receptor (IL-27Ra) and demonstrated that IL-27 signaling in both CD4 and CD8 T cells is important for
diabetes development. Additionally, our preliminary data show that lack of direct IL-27 signaling results in
decreased CD8 T cell frequency, proliferation, and cytokine production in the pancreatic islets. Together these
observations lead us to hypothesize that IL-27 signaling is important for the accumulation and sustained
effector function of autoreactive CD8 T cells. In Aim 1, we will determine the mechanism by which IL-27
signaling directly promotes the accumulation and sustained effector function of autoreactive CD8 T
cells. These experiments will test the intrinsic effect of IL-27 signaling on CD8 T cell homing and differentiation
into pathogenic effectors. In Aim 2, we will determine the mechanism by which direct IL-27 signaling
promotes the ability of CD4 T cells to help autoreactive CD8 T cells. Pathogenic CD8 T cells require help
from CD4 T cells for activation and propagation. Therefore, these experiments will test the effect of CD4 T cell-
intrinsic IL-27 signaling on the differentiation of CD8 T cells in the pancreatic islets. This proposal will advance
our understanding of the differentiation and effector function of autoreactive CD8 T cells during the progression
of T1D. This is in line with the mission of NIDDK, as the results of this project could lead to identification of the
IL-27 signaling pathway as a novel therapeutic target for the treatment or prevention of T1D.

## Key facts

- **NIH application ID:** 9886072
- **Project number:** 5F31DK118786-02
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Ashley Ciecko
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,079
- **Award type:** 5
- **Project period:** 2019-03-01 → 2020-10-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9886072

## Citation

> US National Institutes of Health, RePORTER application 9886072, The role of IL-27 signaling in the accumulation and sustained effector function of autoreactive CD8 T cells in type 1 diabetes (5F31DK118786-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9886072. Licensed CC0.

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