Short Palate, Lung, and Nasal Epithelial Clone1 (SPLUNC1) level determines steroid-resistant airway inflammation in aging

Am J Physiol Lung Cell Mol Physiol. 2021 Dec 1. doi: 10.1152/ajplung.00315.2021. Online ahead of print.ABSTRACTAsthma and its heterogeneity changes with age. Increased airspace neutrophil numbers contribute to severe steroid-resistant asthma exacerbation in the elderly, which correlates with the changes seen in adult asthmatics. However, whether that resembles the same disease mechanism and pathophysiology in aged and adults is poorly understood. Here, we sought to address the underlying molecular mechanism of steroid-resistant airway inflammation development and response to corticosteroid (Dex) therapy in aged mice. To study the changes in inflammatory mechanism, we employed a clinically relevant treatment model of house-dust mite (HDM)-induced allergic asthma and investigated lung adaptive immune response in adults (20-22 weeks) and aged (80-82 weeks) mice. Our result indicates an age-dependent increase in AHR, mixed granulomatous airway inflammation comprising eosinophils and neutrophils, and Th1/Th17 immune response with progressive decrease in frequencies and numbers of HDM-bearing dendritic cells (DC) accumulation in the draining lymph node (DLn) of aged mice as compared with adult mice. RNAseq experiments of the aged lung revealed SPLUNC1 (Short Palate, Lung, and Nasal Epithelial Clone 1) as one of the steroid-responsive genes, which progressively declined with age and further by HDM-induced inflammation. Moreover, we found increased glycolytic reprogramming, maturatio...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Source Type: research