Importantly, the decreased expression of Spns2 in bronchial epithelium of smoke-exposed mice significantly correlated with the reduced macrophage phagocytic activity, supporting a potential role for disrupted epithelial/macrophage cross-talk and S1P transport via Spns2 in the defective macrophage function in COPD. This evidence concerns the gene SPNS2 and chronic obstructive pulmonary disease.