THE ROLE OF SCAVENGER RECEPTOR BI (SR-BI) IN NEUTROPHILIC PHENOTYPE OF ALLERGIC ASTHMA Grant uri icon

abstract

  • Asthma is a disease impacting approximately 300 million people worldwide with at least 250,000 deaths attributed to it each year. ; Asthma is characterized by recurring symptoms of reversible airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. ; The phenotypic heterogeneity of asthma has been investigated over the past few decades to identify the specific underlying cellular and molecular mechanisms. ; Eosinophilic inflammation has long been considered one of the most distinctive hallmarks of asthma; however, 50% of patients with symptomatic asthma exhibit the neutrophilic phenotype. ; Neutrophils accumulate in the airway in more severe forms of asthma that have been associated with unresponsiveness to current therapeutics. ;In addition, neutrophils are even more prominent at the time of acute and near fatal asthma exacerbations. ; However, the potential mechanisms underlying the neutrophilic inflammation in severe asthma remain less defined and need more intensive study. ;Studies have demonstrated that IL-17A, the founding member of the IL-17 family and a key pro-inflammatory cytokine of the Th17 pathway, is involved in the development and persistence of severe asthma. ;IL-17A production by T cells, termed Th17 cells, has previously been reported to drive pulmonary neutrophilia. ; However, the molecular mechanism by which the adaptive immune response is skewed toward Th17 response in neutrophilic asthma still remains elusive. ; Scavenger receptor class B type I (SR-BI) is a multi-recognition receptor that regulates cholesterol trafficking and cardiovascular inflammation. ; SR-BI is expressed on both hematopoietic cells (e.g., macrophages, dendritic cells [DCs], lymphocytes), and a variety of ‘structural cells’ in different organs (e.g., alveolar epithelium, hepatocytes). ; In our lab, we reported that SR-BI dampens the pulmonary innate immune response during bacterial pneumonia, but the role of SR-BI in asthma is unknown. ; This proposal is driven by our novel hypothesis that pulmonary SR-BI expression is protective against Th17 driven neutrophilic asthma. ; This collaborative project will be conducted among Drs. Reece, Mannie, and Gowdy to test the fundamental hypothesis regarding severe asthma phenotype and provide a path to translate novel clinical interventions for severe asthma. ; The results from this project will provide preliminary data for an R15 application between Drs. Reece, Mannie, and Gowdy.

date/time interval

  • January 2017 - March 2017

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