# Role of IL-17+ Autoreactive T Cells in Experimental Autoimmune Uveitis (EAU)

> **NIH NIH R01** · DOHENY EYE INSTITUTE · 2022 · $457,796

## Abstract

Project Description
This application proposes to continue study the immune factors that are important for the pathogenesis of Th17
autoreactive T cells. We have made significant progress in investigating the mechanisms by which pathogenic
Th17 (IL-17+) and Th1 (IFN-γ+) autoreactive T cells cause autoimmune disease, and in studying whether the
regulation of the pathogenic Th17 response differs from that of the Th1 response in the previous funding
period. Our studies demonstrated that enhanced γδ T cell activation is a critical pathologic step response that
leads to Th17 responses, raising the question whether manipulation of γδ T cell activation can prevent
undesired Th17 responses. Based on our new findings that i) regulatory effect of γδ T cells is closely
associated with adenosine; ii) activation of adenosine receptors (ARs) is an important factor of γδ activation,
leading to augmented pathogenic Th17 responses; and iii) reciprocal interactions between γδ T cells and
adenosine-mediated regulation determine the pathogenic Th1 and Th17 responses, we propose to continue
determine the differences in regulatory mechanisms between Th1 and Th17 responses (Aim1) and determine
the mechanism by which adenosine differently regulates Th1 and Th17 autoimmune responses (Aim 2). The
hypothesis of this application is that the dendritic cells are critically involved in γδ-mediated and adenosine-
mediated regulation.  T cells are able to enhance DCs’ ability of promoting Th17 responses and promote the
generation of DC subset(s) that have greater ability of promoting Th17 responses. We will also determine the
mechanism(s) by which adenosine inhibits Th1 responses but enhances Th17 responses. The proposed
studies will exploit available knockout mice lacking A2ARs or CD73 and determine whether the
proinflammatory effect of γδ T cells on the Th17 response is limited if their ability to bind adenosine is reduced,
whether selective A2AR agonists/antagonists can effectively manipulate Th17 responses, whether
manipulation of the enzymatic function of CD73 is effective in controlling the Th17 response, and whether
adenosine degradation enzyme (ADA) and ADA inhibitors are effective in manipulation of the regulatory activity
of γδ T cells and thus Th17 response. Successful accomplishment of the proposed studies should elucidate
the molecular and cellular mechanism by which adenosine regulated autoimmune Th1 and Th17 responses
and further clarify the pathogenic role of, and relationship between, IFN-γ+ and IL-17+ autoreactive T cells in
EAU should contribute to our understanding of the mechanism of autoimmune disease pathogenesis.

## Key facts

- **NIH application ID:** 10319930
- **Project number:** 5R01EY018827-10
- **Recipient organization:** DOHENY EYE INSTITUTE
- **Principal Investigator:** Deming Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $457,796
- **Award type:** 5
- **Project period:** 2009-09-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10319930

## Citation

> US National Institutes of Health, RePORTER application 10319930, Role of IL-17+ Autoreactive T Cells in Experimental Autoimmune Uveitis (EAU) (5R01EY018827-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10319930. Licensed CC0.

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