However, CS-induced pulmonary inflammation was largely improved in SphK2−/− mice, both the CD45+CD11b+ subpopulation and the production of IL-6 and IL-33 decreased, indicating that SphK2 deficiency attenuated pulmonary inflammation and small airways fibrosis, and delayed emphysema pathogenesis possibly by reducing S1P production, blunting the S1P signaling and preserving the pulmonary CFTR function. This evidence concerns the gene CFTR and pulmonary emphysema.