# Immunological Basis of Autoimmune Addison's Disease in a Novel Canine Model System

> **NIH NIH K01** · UNIVERSITY OF MINNESOTA · 2022 · $130,302

## Abstract

Project Summary/Abstract
Autoimmune Addison’s Disease (AAD) is a life-threatening endocrine disorder caused by the immune-
mediated destruction of the adrenal cortex. Affected individuals lack key hormones that are critical for normal
homeostasis. Because of this, patients with AAD are at high risk of developing a potentially deadly adrenal
crisis characterized by hypotensive shock, vomiting, and life-threatening electrolyte abnormalities. Limited
progress has been made over the past half-century in developing new therapies for AAD, in part because there
is no actively studied animal model for the disease. Fortunately, dogs provide an opportunity for this very
purpose. The disease is naturally occurring in both humans and dogs, and shares similar clinical, genetic, and
immunologic underpinnings in both species. The goal of this study is to lay the groundwork for a canine model
system to study AAD by characterizing the antigen-specific T cells that trigger the disease and determining the
peptide sequences recognized by these T cells. Specifically, we will test the hypothesis that AAD is triggered
by IFN-g- producing CD4+ T cells that are activated by peptides derived from steroid-producing enzymes in the
adrenal cortex. Once we have identified and characterized these key players involved in triggering the immune
system dysfunction in AAD, we can begin to develop approaches that manipulate or downregulate the aberrant
immune response. Ultimately, we expect to use this canine model system to drive advances in our
understanding of AAD and to foster the development of novel immunotherapies for humans. The work
proposed in this application will be conducted at the renowned Center for Immunology at the University of
Minnesota, and will provide a critical training opportunity in T cell biology, autoimmune disorders, and the
benchtop methods required to study these topics comprehensively.

## Key facts

- **NIH application ID:** 10310454
- **Project number:** 5K01OD027058-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Steven Gene Friedenberg
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $130,302
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10310454

## Citation

> US National Institutes of Health, RePORTER application 10310454, Immunological Basis of Autoimmune Addison's Disease in a Novel Canine Model System (5K01OD027058-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10310454. Licensed CC0.

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