# Roles of STING and innate lymphoid cell plasticity in severe asthma

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2022 · —

## Abstract

The goal of the proposed research is to identify mechanisms that regulate neutrophilic lung
inflammation and airway hyperresponsiveness (AHR) in a novel severe asthma. New therapeutic targets
are critically needed for non-type 2 or neutrophilic severe asthma. Interleukin-33 (IL-33) drives group 2
innate lymphoid cells (ILC2s) to promote type 2 eosinophilic lung inflammation, but emerging evidence
suggests that significant ILC2 plasticity exists that allows a switch in phenotype to group 1 ILCs (ILC1s)
that promote type 1 inflammation. We have developed a novel innate severe asthma model with
neutrophilic inflammation, high corticosteroid-resistant AHR, ILC2 to ILC1 shift ,and elevated type 1 and
2 interferon levels. We hypothesize that stimulator of interferon genes (STING) regulates the
inflammatory and AHR responses in the model as well as drives ILC plasticity towards an ILC1 phenotype.
We will determine the role of STING in AHR and neutrophilic inflammation in wild type and STING
knockout mice as well as in wild type mice receiving STING antagonists. Further, we will assess co-
blockade of STING and IL-33 as a therapeutic strategy in the model and use adoptive transfer studies to
investigate ILC2 plasticity and the role of ILCs in the severe asthma model phenotype. We will also
identify the cellular sources of STING, including potential novel contributions from ILC expression of
STING. Additionally, we will assess whether type 1 and/or type 2 interferon receptors and STAT1 are
required for features of severe asthma in the model. Finally, we will use human lung and peripheral blood
samples to determine the translational impact of STING in ILC plasticity and evaluate expression levels
of STING-related pathway transcripts in samples from asthmatics and controls. As novel treatments are
needed for severe non-type 2 asthma in Veterans, these studies support STING as a potential candidate
in driving neutrophilic lung inflammation and airway hyperresponsiveness in a severe asthma.

## Key facts

- **NIH application ID:** 10293537
- **Project number:** 5I01BX005073-02
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** TAYLOR A DOHERTY
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10293537

## Citation

> US National Institutes of Health, RePORTER application 10293537, Roles of STING and innate lymphoid cell plasticity in severe asthma (5I01BX005073-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10293537. Licensed CC0.

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