A CCL24-dependent Pathway Augments Eosinophilic Airway Inflammation in House Dust Mite-challenged Cd163(−/−) Mice

CD163 is a macrophage scavenger receptor with anti-inflammatory and pro-inflammatory functions. Here, we report that alveolar macrophages (AMΦs) from asthmatic subjects had reduced cell surface expression of CD163, which suggested that CD163 might modulate the pathogenesis of asthma. Consistent with this, house dust mite (HDM)-challenged Cd163(−/−) mice displayed increases in airway eosinophils and mucous cell metaplasia (MCM). The increased airway eosinophils and MCM in HDM-challenged Cd163(−/−) mice were mediated by augmented CCL24 production and could be reversed by administration of a neutralizing anti-CCL24 antibody. A proteomic analysis identified the calcium-dependent binding of CD163 to Dermatophagoides ptyeronyssinus peptidase 1 (Der p1). Der p1-challenged Cd163(−/−) mice had the same phenotype as HDM-challenged Cd163(−/−) mice with increases in airway eosinophils, MCM and CCL24 production, while Der p1 induced CCL24 secretion by bone marrow-derived macrophages (BMMΦs) from Cd163(−/−) mice, but not BMMΦs from WT mice. Lastly, airway eosinophils and bronchoalveolar lavage fluid CCL24 levels were increased in Der p1-challenged WT mice that received adoptively transferred AMΦ’s from Cd163(−/−) mice. Thus, we have identified CD163 as a macrophage receptor that binds Der p1. Furthermore, we have shown that HDM-challenged Cd163(−/−) mice have increased eosinophilic airway inflammation and MCM that are mediated by a CCL24-dependent mechanism.