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Principal Investigator: Migliaccio, Christopher Todd
Institute Receiving Award University Of Montana
Location Missoula, MT
Grant Number R21ES032910
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 17 Mar 2021 to 29 Feb 2024
DESCRIPTION (provided by applicant): Innate immune cell contribution in wood smoke induced effects to pulmonary function Wildfires are a growing global issue, and a significant concern for public health. Each year, wildfires continue to make headlines as tens of thousands of fires and millions of acres burn around the world. Due to the effects of climate change, these wildfires have become more intense and longer burning. Although wildfires threaten lives directly, and wildfire smoke affects us all—particularly as the intensity and duration of wildfires escalates globally. exciting new preliminary data shows that individuals from a community inundated with hazardous levels of wildfire smoke (daily average: 220.9 µg/m3 of PM2.5) for 49 days exhibited a significant decrease in lung function at least two years after the wildfire event, with a greater effect observed in the older (>65 years) fraction of the cohort. Moreover, we demonstrate pulmonary inflammation and airway hyperreactivity, facilitated by cytokine mediators in our mouse model of acute wood smoke exposure. The objective of this proposal is to determine how wildfire smoke affects components of innate immunity, macrophage subsets and innate lymphoid cells, into generating alarmins and inflammatory mediators that result in tissue remodeling and decreased lung function. We propose the central hypothesis that ILC2 activities are initiated by IL-33 and macrophages in response to wood smoke exposure, resulting in the production and release of inflammatory mediators which trigger pathology. To effectively test this hypothesis, the following specific aims will be addressed: Aim 1: Exposure to WS will result in time-, dose-, age-, and sex-dependent adverse pulmonary effects. Aim 2: Exposure to high levels of wildfire smoke will result in alterations to innate immune components that will promote tissue remodeling in the lungs. The proposed studies will utilize the state-of-the- art Inhalation and Pulmonary Physiology Core facility at the University of Montana to develop a mouse model of the community exposures. Impact Together, the proposed cutting-edge murine studies complementing the ongoing unique longitudinal human studies will have a sustained and powerful impact on wildfire smoke-induced health effects and macrophage immunobiology. The successful completion of the project will provide a significant missing link into a novel mechanism by which the environment adversely affects respiratory health, and also provide a link to how other environmental pollutants (e.g. cigarette smoke, diesel exhaust, particulate matter) may serve as risk factors for diminished lung function. Lastly by understanding how macrophage subsets influence inflammatory responses in ILC2s, therapeutic approaches can be developed with greater precision and efficacy, thereby significantly advancing treatment options for this growing public health concern.
Science Code(s)/Area of Science(s) Primary: 69 - Respiratory
Secondary: 03 - Carcinogenesis/Cell Transformation
Publications No publications associated with this grant
Program Officer Srikanth Nadadur
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