# Regulation of salivary gland inflammation in Sjogren's Syndrome by Annexin 1

> **NIH NIH R21** · ADA FORSYTH INSTITUTE, INC. · 2020 · $298,500

## Abstract

PROJECT SUMMARY
This objective of this proposal is to examine the specific role of the anti-inflammatory and pro-resolving protein
Annexin A1 (AnxA1) during the development and onset of Sjögren's Syndrome (SjS), the second most common
rheumatic disease that primarily targets the salivary and lacrimal glands causing clinical dry eye and dry mouth
symptoms. Pathophysiological events in SjS are strongly associated with aberrant proteolysis. The proposal
hypothesizes that SjS-associated proteolytic processing alter the anti-inflammatory and pro-resolution properties
of AnxA1. While loss of AnxA1 has been associated with uncontrolled proliferation and activation of autoreactive
Th17 cells in the mouse model of experimental autoimmune uveitis, there is a critical knowledge gap about
AnxA1 in the SjS disease process. In our preliminary studies, we discovered cleavage products of the N-terminal
region of AnxA1 that harbors the main pharmacophore for the anti-inflammatory properties of AnxA1. Aim 1 will
determine whether preventive treatment with N-terminal AnxA1 peptide ac2-26 will reduce inflammation,
modulate T cell response and prevent salivary gland destruction in the NOD mouse model. Aim 2 will evaluate
the effect of AnxA1-protective protease inhibitors on the development and onset of SjS in NOD mice. Results
from this study will provide critical insights into the role of AnxA1 in modulating autoimmune response and
promote resolution in SjS and suggest novel mechanism-derived strategies for diagnosis and controlling
inflammation and tissue dysfunction and destruction in SjS.

## Key facts

- **NIH application ID:** 9954019
- **Project number:** 5R21DE029003-02
- **Recipient organization:** ADA FORSYTH INSTITUTE, INC.
- **Principal Investigator:** Markus Hardt
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $298,500
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954019

## Citation

> US National Institutes of Health, RePORTER application 9954019, Regulation of salivary gland inflammation in Sjogren's Syndrome by Annexin 1 (5R21DE029003-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9954019. Licensed CC0.

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