Wednesday, November 19, 2025 11/19/2025

Allergen-induced extracellular DNA in type 2 immunity

Award Number: R01AI169530
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/21/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2027

Group Awards By:

View Award Description

Allergen-induced extracellular DNA in type 2 immunity - PROJECT SUMMARY/ABSTRACT The long-term objective of this project is to investigate the fundamental immunological mechanisms involved in the development of asthma and allergic airway diseases. Various atmospheric factors contribute to the pathogenesis of these diseases, including viral infection, allergen exposure, and air pollution. It is becoming increasingly clear that the airway epithelium plays a key role in orchestrating immune responses in the airways. Nonetheless, the mechanisms involved in the initiation and development of immune responses to environmental factors are not fully understood. Sensing of self-DNA by immune cells has been implicated in sterile inflammation in various organs and the pathophysiology of diseases. We recently found that human airway epithelial cells rapidly release fragments of nuclear DNA into the extracellular milieu following allergen exposure in vitro. Caspase-3 was rapidly activated in airway epithelial cells upon allergen exposure without apparent signs of cellular apoptosis or necrosis. Self- DNA was also released into the airway lumen in naïve mice exposed to allergens in vivo, and blocking extracellular DNA (eDNA) suppressed type 2 immune responses to the allergens. Therefore, we hypothesize that allergen-induced rapid extracellular release of self-DNA by airway epithelial cells promotes type 2 immune responses to airborne allergens. The experiments described in this proposal will investigate this hypothesis by focusing on two fundamental questions. In Aim 1, we will determine how DNA is rapidly released by airway epithelial cells in response to allergen exposure in vitro. We will examine the mechanisms of non-canonical activation of caspase-3 and calpains, which initiate and terminate active DNA release, respectively. In Aim 2, we will determine how epithelium-derived eDNA promotes type 2 immunity and allergic airway inflammation in vivo. We will investigate the role of the pattern recognition receptor for advanced glycation endproducts (RAGE) in sensing eDNA and leading exaggerated effector functions of group 2 innate lymphoid cells and CD4+ T cells. We will employ a combination of complementary expertise in cellular and molecular biology of airway epithelial cells and immunology and disease models of type 2 immunity in the laboratories of Dr. O’Grady and Dr. Kita, respectively. Novel and robust in vitro and in vivo models have been developed for this project. These studies will provide a better understanding of how airway epithelium responds to environmental allergens and will define the key molecules responsible for type 2 immune responses in the airways. Ultimately, these studies will characterize the critical mechanism(s) involved in allergen-induced immune responses, allowing for the identification of novel therapeutic target(s) for treating and ideally preventing immune-mediated airway diseases, such as asthma, chronic rhinosinusitis, and other allergic disorders.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $1,247,804 )
2025	2025	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Allergy and Infectious Diseases Research	001	4	8/21/2025	EXTENSION WITH OR WITHOUT FUNDS	$1,247,804
2025	2024	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Allergy and Infectious Diseases Research	000	3	8/21/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,247,804

Issue Date FY: 2024 ( Subtotal = $631,168 )
2024	2024	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Allergy and Infectious Diseases Research	000	3	7/17/2024	NON-COMPETING CONTINUATION	$631,168
														Subtotal = $631,168

Issue Date FY: 2023 ( Subtotal = $635,887 )
2023	2023	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Allergy and Infectious Diseases Research	000	2	7/12/2023	NON-COMPETING CONTINUATION	$635,887
														Subtotal = $635,887

Issue Date FY: 2022 ( Subtotal = $649,135 )
2022	2022	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Allergy and Infectious Diseases Research	000	1	9/21/2022	NEW	$649,135
														Subtotal = $649,135

Grand Total All Awards = $3,163,994

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Allergen-induced extracellular DNA in type 2 immunity

Award Number: R01AI169530

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/21/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer