Immunological and Social Determinants of Asthma: From Cytokine Signaling to Air Pollution Disparities

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Date
2024-10
Language
American English
Embargo Lift Date
2025-05-04
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Degree
Ph.D.
Degree Year
2024
Department

Microbiology & Immunology
Grantor
Indiana University
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Abstract

Asthma is a chronic respiratory disease characterized by airway inflammation and hyperresponsiveness, impacting 262 million individuals globally. This heterogeneous condition results from a complex interplay of genetic, environmental, and social factors. The pathophysiology involves dysregulated immune responses, particularly through cytokine signaling, and is exacerbated by environmental pollutants and social determinants of health (SDOH). This thesis aims to (1) elucidate novel cytokine signaling pathways involved in asthma, specifically a potential type II IL-9 receptor complex, and (2) evaluate the impact of California's Assembly Bill 617 (AB 617) on reducing air pollution and asthma disparities in disadvantaged communities. The research employs molecular biology techniques, including flow cytometry, proximity ligation assay, and RNA sequencing, to investigate IL-9 signaling in airway epithelial cells. It also involves a policy analysis of AB 617's initial effectiveness in reducing fine particulate matter (PM2.5) levels and asthmaassociated emergency room (ER) visits through environmental monitoring and hospital records. The study identifies a novel type II IL-9 receptor complex composed of IL-9Rα and IL-13Rα1, suggesting new therapeutic targets for asthma management. Policy analysis reveals limited initial success of AB 617 in reducing air pollution and asthma incidence, highlighting the need for enhanced regulatory measures and community engagement. Understanding the molecular mechanisms of IL-9 signaling and addressing environmental and social determinants are crucial for comprehensive asthma management. Integrating scientific research with policy interventions can improve health outcomes and reduce disparities in asthma prevalence and severity.

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