Asthma is a lung disease that is growing in prevalence and disproportionately affects children. Many asthmatics show underlying allergic inflammation that is thought to trigger their symptoms, and suppressing inflammation shows efficacy in treating disease. However, the mechanism by which allergen inhaled into the lung actually initiates inflammatory responses is poorly understood. In particular, the allergen must be taken up by so-called professional antigen presenting cells to be presented to CD4 T cells, yet the uptake of allergen from the airway lumen has not been well characterized. In preliminary studies, we have identified a subset of macrophages which appear to be the main allergen capturing cells near the bronchi, where inflammation develops. These bronchus-associated macrophages are phenotypically distinct from alveolar macrophages in the distal airways as well as from classical dendritic cells. The overall goal of this proposal is to determine whether bronchus-associated macrophages are important for the allergic inflammation near the bronchial tree.
The specific aims are to 1) characterize the distinct features and cellular interactions of bronchus-associated macrophages compared with classical dendritic cells and 2) assess the impact of deficiency in bronchus- associated macrophages on allergic lung inflammation. We believe these studies will provide important new insights into the mechanism by which allergen is taken up from the bronchi in the initiation of allergic lung inflammation, which may have important implications for understanding the pathogenesis of asthma.

Public Health Relevance

Asthma is a lung disease affecting tens of millions of people in the US and is growing in prevalence. Allergic inflammation plays a key role in most cases of asthma, yet the mechanisms initiating this inflammatory response remain poorly understood. In this project, we will explore the role of a population of macrophages surrounding the lung airways in the initiation of allergic lung inflammation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI130495-01A1
Application #
9387774
Study Section
Special Emphasis Panel (ZRG1-IMM-T (90))
Program Officer
Davidson, Wendy F
Project Start
2017-06-07
Project End
2019-05-31
Budget Start
2017-06-07
Budget End
2018-05-31
Support Year
1
Fiscal Year
2017
Total Cost
$234,712
Indirect Cost
$84,712
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118