# Cul5 and Triad1 partner to prevent T cell mediated lung inflammation and asthma

> **NIH NIH R03** · CHILDREN'S HOSP OF PHILADELPHIA · 2020 · $78,880

## Abstract

Abstract
Asthma is a chronic inflammatory disease of the airways that affects 26 million Americans and results in
approximately 3600 deaths per year in the US alone (1a). Asthma is a heterogeneous disease and both Th2
predominant and Th17 predominant forms have been described with different etiologies. Interestingly, it was
recently determined that a subset of patients with particularly severe asthma contain T cells that make both Th2
and Th17 cytokines. However, mechanisms that prevent allergen specific T cells from becoming Th2/17 dual
producers have not been described. We have identified a novel inhibitory pathway that limits the differentiation
and pathogenicity of both Th2, Th9 and Th2/17 dual-producing T cells and protects against airway remodeling
in mice. This pathway is controlled by the E3 ubiquitin ligase Cul5. Supporting this, we recently generated mice
in which Cul5 was deleted only in T cells, and determined that Cul5 limits the numbers of Th2, Th9 and Th2/17
dual cytokine producing T cells and airway remodeling after house dust mite exposure. Specifically, we found
that mice lacking Cul5 in T cells showed increased lung inflammation, eosinophilia, goblet cell hyperplasia and
fibrosis, as well as AHR. Using a screen to reveal Cul5 binding partners, we identified Traid1, a RING-between-
RING E3 ubiquitin ligases that was recently shown to be important for Cul5 activity. Based on these preliminary
data we hypothesize that Cul5 works with Triad1 to limit the numbers of pathogenic T cells to prevent
asthma. Our long term goal is to develop novel therapeutic strategies that activate the Cul5 pathway to turn T
cells off in patients with asthma. However, to do this effectively we must first determine how Cul5 activity is
regulated. In this proposal we will determine whether mice with a deletion of Traid1 in T cells develop a similar
inflammation and airways remodeling following HDM exposure as we observed in Cul5fl/flCD4-Cre animals. This
would indicate that regulating the interaction between Cul5 and Triad1 might be a good therapeutic approach.

## Key facts

- **NIH application ID:** 9874071
- **Project number:** 1R03AI148884-01
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Paula Maria Oliver
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $78,880
- **Award type:** 1
- **Project period:** 2020-01-29 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9874071

## Citation

> US National Institutes of Health, RePORTER application 9874071, Cul5 and Triad1 partner to prevent T cell mediated lung inflammation and asthma (1R03AI148884-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9874071. Licensed CC0.

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