ArticleAmerican journal of physiology. Lung cellular and molecular physiology2022
Short palate, lung, and nasal epithelial clone 1 (SPLUNC1) level determines steroid-resistant airway inflammation in aging.
Article in American journal of physiology. Lung cellular and molecular physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- SPLUNC1/BPIFA1 Restrains Neutrophil-Dominant Inflammation and Coordinated Inflammatory Gene Programs During LPS-Induced Lung Injury.Biomolecules · 2026Article
- Article
- Immune activation and mucin dysregulation in pediatric refractoryFrontiers in cellular and infection microbiology · 2025Article
- UBR5 metabolically reprograms nasopharyngeal carcinoma cells to promote glycolysis and M2 polarization via SPLUNC1 signaling.NPJ precision oncology · 2024Article
- Aging-Related Mechanisms Contribute to Corticosteroid Insensitivity in Elderly Asthma.International journal of molecular sciences · 2023Review
- SPLUNC1 regulates LPS-induced progression of nasopharyngeal carcinoma and proliferation of myeloid-derived suppressor cells.Medical oncology (Northwood, London, England) · 2022Article
- Immunosenescence: A Critical Factor Associated With Organ Injury After Sepsis.Frontiers in immunology · 2022Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Asthma and its heterogeneity change with age. Increased airspace neutrophil numbers contribute to severe steroid-resistant asthma exacerbation in the elderly, which correlates with the changes seen in adults with asthma. 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 used a clinically relevant treatment model of house-dust mite (HDM)-induced allergic asthma and investigated lung adaptive immune response in adult (20-22 wk old) and aged (80-82 wk old) mice. Our result indicates an age-dependent increase in airway hyperresponsiveness (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. RNA-Seq experiments of the aged lung revealed short palate, lung, and nasal epithelial clone 1 (SPLUNC1) as one of the steroid-responsive genes, which progressively declined with age and further by HDM-induced inflammation. Moreover, we found increased glycolytic reprogramming, maturation/activation of DCs, the proliferation of OT-II cells, and Th2 cytokine secretion with recombinant SPLUNC1 (rSPLUNC1) treatment. Our results indicate a novel immunomodulatory role of SPLUNC1 regulating metabolic adaptation/maturation of DC. An age-dependent decline in the SPLUNC1 level may be involved in developing steroid-resistant airway inflammation and asthma heterogeneity.
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