We have identified that apolipoprotein E serves as an endogenous negative regulator of airway hyperreactivity and goblet cell hyperplasia in asthma by a low density lipoprotein receptor(LDLR)-dependent mechanism (Apolipoprotein E Negatively Regulates House Dust Mite-induced Asthma via a LDL Receptor-mediated Pathway. Yao X, Fredriksson K, Yu ZX, Xu X, Raghavachari N, Keeran KJ, Zywicke GJ, Kwak M, Amar MJ, Remaley AT, Levine SJ. Am J Respir Crit Care Med. 2010 Jul 9. Epub ahead of print). The effects of apoE, which is synthesized by macrophages in the lung, are mediated via binding to LDLRs that are expressed on ciliated airway epithelial cells. This project will utilize apolipoprotein receptor knock-out mice to define the role of other apolipoprotein receptors in modulating the pathogenesis of asthma. Furthermore, the mechanisms by which asthma pathogenesis is modulated by lung apolipoprotein receptors will be characterized. This research has identified (1) a novel role for the very low density lipoprotein receptor in allergic asthma by regulating dendritic cell function. In particular, we have shown that the very low density lipoprotein receptor is expressed by circulating human dendritic cells (DC) and attenuates DC-mediated adaptive immune responses in HDM-induced airway inflammation (Journal of Immunology 2014;192: 4497) and (2) the interaction between apolipoprotein A-I and its receptor, the ABCA1 transporter, attenuates ovalbumin-induced neutrophilic airway inflammation by suppressing granulocyte colony-stimulating factor production by pulmonary vascular endothelial cells and alveolar macrophages (Am J Respir Cell Mol Biol, 2014, in press).
