# Investigation of Dpp9 in COVID19

> **NIH NIH R21** · YALE UNIVERSITY · 2024 · $209,162

## Abstract

Project Summary
To better understand the determinants of severe COVID19, we have focused on the inflammasome regulatory
protein DPP9. GWAS have implicated DPP9 in poor outcomes in COVID19 and in the development of idiopathic
pulmonary fibrosis. DPP9 and closely related DPP8 serve as endogenous inhibitors of the viral inflammasome
sensors NLRP1 and CARD8. This pathway is activated by diverse mechanisms of pathogen sensing which
include detection of viral encoded proteases, bacterial E3 ubiquitin ligases and direct sensing of viral dsRNA.
Our preliminary data indicate that this pathway is transcriptionally upregulated in human myeloid cells in
response to SARS-CoV-2, a stimulus which activates the inflammasome. We have also discovered that mice
which lack Dpp8 and Dpp9 have dysregulated T cell responses and develop more severe disease when
challenged with SARS-CoV-2. Our ongoing work seeks to better understand 1) the immunological differences
conferred by the COVID19 risk allele rs2109069 “A” located within a DPP9 intronic region, 2) the basis for T cell
dysregulation in our novel mouse model and 3) how T cell dysfunction influences disease severity in response
to SARS-CoV-2 infection.

## Key facts

- **NIH application ID:** 10864020
- **Project number:** 5R21AI178249-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Richard A Flavell
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $209,162
- **Award type:** 5
- **Project period:** 2023-06-09 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10864020

## Citation

> US National Institutes of Health, RePORTER application 10864020, Investigation of Dpp9 in COVID19 (5R21AI178249-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10864020. Licensed CC0.

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