Coactosin-Like Protein Reduces Prostaglandin D(2) Production in Alveolar Macrophages and Alleviates Allergic Airway Inflammation.

Allergic asthma is a significant global health issue characterized by chronic airway inflammation. Current treatments only alleviate symptoms but fail to cure the disease due to its complex pathology. Lipid mediators from arachidonate metabolism are pivotal in immune regulation in asthma. Previously, coactosin-like protein (CLP) is identified as a regulator of leukotriene production in vitro. However, its role in asthma is unclear. In this study, it is found that CLP-deficient (Cotl1(-/-)) mice challenged with house dust mite (HDM) exhibits exacerbated airway inflammation, macrophage polarization, and type 2 immune responses. CLP deficiency increased prostaglandin D(2) (PGD(2)) in bronchoalveolar lavage (BAL) and alveolar macrophages (AMs), activating the PGD(2) receptor chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) on immune cells. Notably, HDM exposure reduced pulmonary CLP levels in wild-type (WT) mice, and overexpression of CLP in Cotl1(-/-) macrophages decreased HDM-induced PGD(2) in BAL and alleviated inflammation. Cotl1(-/-) AMs exacerbated HDM-induced airway inflammation compared to WT AMs, and this effect is dependent on CRTH2 signaling. These findings reveal that CLP modulates macrophage polarization and suppresses the PGD(2)-CRTH2 pathway to alleviate airway inflammation, highlighting CLP as a promising therapeutic target for asthma.