Novel role for scavenger receptor B-I in neutrophilic asthma (IRC10P.419)

Abstract

Abstract Asthma is a heterogeneous airway disease that has risen significantly in recent decades. While there has been a major research focus on eosinophilic asthma, the neutrophilic, Th17-predominant disease that characterizes severe asthmatics is less understood. Scavenger Receptor B-I (SR-BI) is a receptor mostly studied in the context of cellular uptake of cholesterol. Recently, we reported that SR-BI regulates the pulmonary innate immune response, but the role of SR-BI in asthma is unknown. Therefore, SR-BI+/+ and SR-BI-/- mice were sensitized on days 0 and 7 by oropharyngeal aspiration of ovalbumin (OVA) together with LPS and then challenged on day 14 with an aerosol OVA. Airway inflammation and cytokines were quantified 48hrs after challenge. Bone marrow-derived dendritic cells (BMDCs) from SR-BI+/+ and SR-BI-/- mice were co-cultured in the presence of OVA/LPS with CD4+ T cells from OT-II mice that carry a transgenic TCR specific for the MHC class II-restricted OVA peptide (OT-II Tg). Compared to SR-BI+/+ counterparts, SR-BI-/- mice had increased pulmonary neutrophils, Th17 cells, G-CSF and CXCL5 after OVA challenge, but had equivalent amounts of IL-4, IL-5, and eosinophils. BMDCs from SR-BI-/- mice have elevated levels of CD80 and CD86, and CD4+ OT-II Tg T cells produced more IL-17 after culture with OVA/LPS. SR-BI modulates the lung’s response to environmental adjuvants such as LPS by regulating Th17 polarization, suggesting a novel role for SR-BI in neutrophilic asthma.