Epithelial immune responses during respiratory viral exacerbation of asthma

Active Cooperative Agreement Awarded Last action

Award ID
U19AI175089
Recipient
Awarding agency
Obligated
$6,305,089

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 72% complete
Place of performance
Seattle, WA 98109, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Lower respiratory tract viral infections serve as the dominant trigger for the onset and progression of asthma. Although asthma management has shifted towards targeting airway inflammation at all levels of the disease, primarily with inhaled corticosteroids (ICS) and biologic therapies targeting type-2 (T2) inflammation, there is a substantial burden of disease that is not responsive to these therapies. Specifically, a substantial portion of individuals treated with ICS therapy have persistent T2 inflammation in their lower airways and a large and growing portion of individuals with asthma have inflammation of the airways that is not T2 predominant (non- T2). These related phenomena of persistent T2 (T2-HIGH) and non-T2 inflammation in asthma are emerging as the most common phenotypes in adults, and now make up a substantial portion of children with the disease. The mechanisms responsible for persistent T2 and non-T2 inflammation are incompletely understood, but there is strong evidence that the epithelium and epithelial-derived cytokines play a major role in the immunology of asthma, and we have recently demonstrated that the epithelium is infiltrated with specific innate immune cells that interact with the epithelium to propagate and regulate inflammation. Our central hypothesis is that the airway epithelium serves as a central coordinator of the immune response to viral respiratory tract infection in asthma. Further, airway epithelial cells (AECS) from T2-HIGH and non-T2 individuals differentially interact with immune cells to support inflammation in a manner that can be identified and targeted. We have an established program to isolate AECS from children and adults to examine the function of these cells in asthma using a combination of organotypic cell culture models, often in combination with immune cells. The primary goals of the seattle center are to identify primary alterations in AECS in asthma, understand how AECS differ between T2-HIGH and non-T2 individuals, and characterize interactions between the epithelium and immune cells that are in close proximity. In project 1, we examine the underpinnings of persistent T2 inflammation mediated through mast cells and eosinophils acting in conjunction with the epithelium and the components of this inflammation that are resistant to corticosteroids. In project 2, we examine the basis of interactions between the epithelium and macrophages, TH17 cells, and neutrophils and how epithelial cells from each of the groups support inflammation through these cells. These projects are supported by pediatric and adult epithelial cores (core B) to isolate AECS from well phenotyped adults and children and further examine connections between phenotype, genomics, genotype, and clinical outcome. The studies are supported by an advanced bioinformatics core (core C) using state of the art single cell and bulk RNA sequencing. These studies will facilitate the precise targeting of inflammation based on clinical phenotype and epithelial endotype and a greater understanding of the basis of interactions between the epithelium and immune cells that reside within the epithelium in asthma.

Transactions

Action Obligated Date
Amendment $1,487,760
Amendment $1,517,172
Amendment $0
Amendment $0
Amendment $1,615,395
Original award $1,684,762

Subawards

Subrecipient Amount Awarded
Benaroya Research Institute At Virginia Mason Epithelial Immune Responses During Respiratory Viral Exacerbation of Asthma. $18,934
Seattle Children's Hospital $300,255
Seattle Children's Hospital $265,428
Benaroya Research Institute At Virginia Mason $21,205
Benaroya Research Institute At Virginia Mason $27,094
Seattle Children's Hospital $266,682
Seattle Children's Hospital $364,692
Benaroya Research Institute At Virginia Mason $269,232
Seattle Children's Hospital $383,929
Benaroya Research Institute At Virginia Mason $23,281
Seattle Children's Hospital $267,864
Benaroya Research Institute At Virginia Mason $7,305
Show all 12

Quick answers

Who received award U19AI175089?

U19AI175089 was awarded to University Of Washington by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on April 25, 2023.

How much is award U19AI175089 worth?

$6,305,089 has been obligated on U19AI175089.

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