# Immune Function and the Progression to Type 1 Diabetes

> **NIH NIH P01** · UNIVERSITY OF FLORIDA · 2022 · $1,279,702

## Abstract

PO1 SUMMARY / ABSTRACT
Type 1 diabetes (T1D) is a disorder that arises following the autoimmune destruction of insulin producing
pancreatic β-cells. Previous studies, including nearly 250 peer reviewed articles supported by this P01 since its
genesis some two decades ago, demonstrated that individuals with- or at increased-risk for T1D display a
series of innate and adaptive immunological abnormalities, as well as genetic-based aberrancies, that were
associated with disease susceptibility. These efforts have identified a variety of immune dysfunctions
associated with T1D including but not limited to “Interferonopathy” - defined as the elevated production of and
response to Type 1 interferons, impaired function of regulatory T cells (Treg), and abnormal immune cell:cell
interactions that not only drive autoimmunity in T1D but in addition, are strongly influenced by genetics (e.g.,
loss/gain of functional mutations, shifts in exon usage). Yet the contributions of T1D-risk loci to these
processes remain quite unclear. Thus, our goal in seeking renewal of this P01 is to elucidate the mechanisms
by which T1D-associated genes both generally (Projects 2 and 3) and specifically; IFIH1, TYK2 (Project 1),
and IKZF4 (Project 3), impart functional immunoregulatory abnormalities (Project 2) that result in expansion of
self-reactive adaptive immune cells, defective regulatory/effector mechanisms in T cells, inflammatory antigen
presenting cells (APC), abnormal immune function in specific cell types, unusual patterns of lymphoid
development, and inappropriate responses of β-cells to danger/inflammatory signals. These activities will
collectively test the P01's overall hypothesis that defects in genetic and immunologic pathways are key to
engender the autoimmune destruction of pancreatic β-cells that results in T1D. This P01 will examine this
hypothesis through three separate but highly interactive Projects that (importantly) have a strong history of
sharing data, using innovative technologies, and assess fresh and cryopreserved samples from well
characterized human subjects with or at risk for T1D as ascertained through two Core facilities: Core A -
Administrative Core and Core B - Laboratory Core. These proposed studies are further supported by the rich
environment for T1D research at the University of Florida that includes resources such as pancreatic and
lymphoid tissue samples from the Network for Pancreatic Organ donors with Diabetes Network (nPOD),
interactions with major disease networks including the NIH Immune Tolerance Network and TrialNet, and
special efforts related to the impact of race (as determined through highly active recruiting efforts) on the
growing notion of T1D heterogeneity. The successes expected from the proposed studies should: 1) provide
novel insights into the immune and genetic influences that contribute to T1D; 2) provide novel biomarkers for
disease susceptibility and autoimmune activity associated with the disease, and could; 3)...

## Key facts

- **NIH application ID:** 10412996
- **Project number:** 5P01AI042288-24
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** MARK A. ATKINSON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,279,702
- **Award type:** 5
- **Project period:** 1997-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412996

## Citation

> US National Institutes of Health, RePORTER application 10412996, Immune Function and the Progression to Type 1 Diabetes (5P01AI042288-24). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10412996. Licensed CC0.

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