Short palate, lung, and nasal epithelial clone 1 (SPLUNC1) level determines steroid-resistant airway inflammation in aging.
Aging
/ pathology
Animals
Antigen Presentation
/ drug effects
Cell Movement
/ drug effects
Dendritic Cells
/ drug effects
Dermatophagoides pteronyssinus
/ drug effects
Dexamethasone
/ pharmacology
Eosinophils
/ drug effects
Epithelial Cells
/ drug effects
Glycolysis
/ drug effects
Glycoproteins
/ metabolism
Granuloma
/ pathology
Inflammation
/ pathology
Lymph Nodes
/ pathology
Mediastinum
/ pathology
Models, Biological
Phosphoproteins
/ metabolism
Respiratory System
/ parasitology
Steroids
/ pharmacology
INTRODUCTION
SPLUNC1
aging
airway inflammation
dendritic cells
steroid-resistant asthma
Journal
American journal of physiology. Lung cellular and molecular physiology
ISSN: 1522-1504
Titre abrégé: Am J Physiol Lung Cell Mol Physiol
Pays: United States
ID NLM: 100901229
Informations de publication
Date de publication:
01 01 2022
01 01 2022
Historique:
pubmed:
2
12
2021
medline:
16
2
2022
entrez:
1
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34851736
doi: 10.1152/ajplung.00315.2021
pmc: PMC8759962
doi:
Substances chimiques
Bpifa1 protein, mouse
0
Glycoproteins
0
Phosphoproteins
0
Steroids
0
Dexamethasone
7S5I7G3JQL
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
L102-L115Subventions
Organisme : NIAID NIH HHS
ID : R03 AI153794
Pays : United States
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