Vitamin D attenuates airway inflammation and airway responsiveness in T2-low asthma by suppressing autophagy via the mTOR signaling pathway

<bold>Background:</bold> The relationship between vitamin D and asthma varies in T2-high and T2-low asthma endotypes, with vitamin D deficiency more significantly impacting airway obstruction in T2-low asthma. <bold>Objective:</bold> To explore the mechanisms behind vitamin D's role in T2-low asthma, and its functions in airway epithelial cells. <bold>Methods:</bold> We studied female BALB/c mice and their offspring, feeding them diets with varying levels of vitamin D for 8 weeks. Post-weaning, offspring continued these diets. T2-low asthma was induced using ovalbumin (OVA) sensitization/challenge combined with ozone exposure (OVA+ozone). We assessed inflammatory cell infiltration, mucus secretion, and resistance using hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and lung function tests. An in vitro model involved stimulating airway epithelial cells with IL-13 and H₂O₂. Effects of vitamin D on mTOR-related proteins were analyzed using Western blot. <bold>Results:</bold> Mice on the LVD diet displayed increased airway inflammation, mucus production, airway remodeling, and resistance in the OVA+ozone group. Elevated levels of autophagy-related proteins and inflammatory cytokines were observed, implicating mTOR-dependent signaling. Vitamin D supplementation in vitro promoted cell migration and reduced IL-13 and H₂O₂-induced ICAM-1 expression, modulating autophagy via the mTOR pathway. <bold>Conclusions:</bold> Our findings suggest a potential mechanism for vitamin D in protecting against T2-low asthma, involving autophagy regulation through the mTOR signaling pathway.