# Single Cell Genomics to Resolve Control of Immune Cell Function During Type 1 Diabetes

> **NIH NIH R21** · NATIONAL JEWISH HEALTH · 2023 · $219,685

## Abstract

PROJECT SUMMARY
 T cells specific for pancreatic beta cell antigens drive an autoimmune response leading to type 1 diabetes
(T1D). During the onset of T1D, many immune cell types infiltrate into pancreatic islets, but the infiltration of each
individual islet varies substantially within an individual mouse or human. Additionally, the interactions between
immune cells and resident islet cells vary over the immune response within the microenvironment of an individual
islet from infiltration and initial activation to a period of regulation before eventual destruction. A better
understanding of factors that control autoreactive T cell function in the islets could lead to therapies for T1D that
target the underlying mechanisms that cause disease. Based on our published work and new preliminary data,
our central hypothesis is that autoreactive CD8+ T cell destruction of beta cells is determined by activation of the
basic region leucine zipper (bZIP) transcription factors in response to the islet antigens and the local cellular
microenvironment. We predict that these programs are differentially induced in CD8+ T cells by the cellular
microenvironment of each individual islet. We propose two aims to test these predictions during onset of T1D in
NOD mice using novel single cell functional genomics approaches. In Aim 1 we will determine the contribution
of the bZIP transcription factors family to autoreactive T cell function in the pancreas. In Aim 2 we will determine
impact of macrophages on the transcriptional programs of individual cells between separate pancreatic islet
microenvironments. The expected results of our study will address unanswered questions about the fundamental
mechanisms controlling T cell activity and immune cell interplay during autoimmune disease.

## Key facts

- **NIH application ID:** 10728072
- **Project number:** 1R21AI178618-01
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** Rachel S Friedman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $219,685
- **Award type:** 1
- **Project period:** 2023-06-26 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10728072

## Citation

> US National Institutes of Health, RePORTER application 10728072, Single Cell Genomics to Resolve Control of Immune Cell Function During Type 1 Diabetes (1R21AI178618-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10728072. Licensed CC0.

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