# GLP-1R agonist immune targets in lean and obesity-associated asthma

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $746,134

## Abstract

Project Summary
Multiple preclinical and clinical studies show that glucagon-like peptide-1 receptor (GLP-1R) agonists, FDA
approved agents used in type 2 diabetes, obesity, and cardiovascular risk reduction, are a promising novel
treatment strategy for asthma. However, the key cellular targets and mechanisms by which GLP-1R agonists
reduce airway inflammation in asthma remain poorly understood. The rationale for the proposed research is
that a better understanding of the cellular targets and anti-inflammatory mechanisms of GLP-1 signaling is
required in order to maximize the clinical use of GLP-1R agonists for the treatment of both lean and obese
patients with asthma. The overall objective in this proposal is to identify the direct immunologic mechanisms by
which GLP-1 signaling reduces inflammation to inform the clinical repurposing of GLP-1R agonists in asthma.
The central hypothesis, based on preliminary data generated in the investigators’ laboratories, is that GLP-1R
agonists directly attenuate both type (T)2 and non-T2 cells and mediators in asthma. Guided by robust
preliminary data which supports that GLP-1R signaling regulates the function of specific human immune cells,
we will test our central hypothesis in two distinct, but highly integrated specific aims. We will determine the anti-
inflammatory role of GLP-1 signaling in 1) platelet-derived T2 and non-T2 inflammation and 2) CD4+ T cell
function in asthma. In aim 1, we will evaluate platelets from lean and obese asthma patients to determine the
role of GLP-1 signaling on platelet inflammatory mediator release (aim 1a). We will assess platelet aggregation
as a biomarker of the inflammatory and clinical response to GLP-1R agonist therapy (aim 1b), and the effect of
GLP-1R agonist therapy on platelet activation and platelet-leukocyte formation in patients with asthma (aim
1c). In aim 2, we will evaluate CD4+ T cells and platelet-adherent CD4+ T cells from lean and obese asthma
patients to determine the role of GLP-1 signaling on CD4+ T cell subset differentiation (aim 2a). We will assess
the effect of GLP-1R agonist therapy on CD4+ T cell activation in patients with asthma (aim 2b). This proposal
capitalizes on sample collection and mechanistic and clinical data from the investigator’s ongoing randomized
controlled trial of a GLP-1R agonist in asthma with comorbid obesity. This fully human approach is innovative
because it defines how GLP-1R agonists regulate multiple key immune cell populations, independent of GLP-
1R agonist effects on comorbid metabolic disease. This proposal is significant because it defines a precision
medicine approach for repurposing GLP-1R agonists in both lean and obese patients with asthma. This study
will inform the use of GLP-1R agonists in asthma and other inflammatory diseases in the absence of metabolic
comorbidity.

## Key facts

- **NIH application ID:** 10856599
- **Project number:** 1R01AI182159-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Katherine N Cahill
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $746,134
- **Award type:** 1
- **Project period:** 2024-08-16 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10856599

## Citation

> US National Institutes of Health, RePORTER application 10856599, GLP-1R agonist immune targets in lean and obesity-associated asthma (1R01AI182159-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10856599. Licensed CC0.

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