Sposito, Francesca 
ORCID: 0009-0007-0272-0318, Pennington, Shaun H, A W David, Christopher, Duggan, Jack, Northey, Sarah, Biagini, Giancarlo, Liptrott, Neill J ORCID: 0000-0002-5980-8966, Charras, Amandine ORCID: 0000-0001-6760-5459, McNamara, Paul S ORCID: 0000-0002-7055-6034 and Hedrich, Christian M ORCID: 0000-0002-1295-6179
(2023)
Age differential CD13 and interferon expression in airway epithelia affect SARS-CoV-2 infection - effects of vitamin D.
Mucosal immunology, 16 (6).
S1933-0219(23)00064-8-S1933-0219(23)00064-8.
Abstract
Young age and high vitamin D plasma levels have been associated with lower SARS-CoV-2 infection risk and favourable disease outcomes. This study investigated mechanisms associated with differential responses to SARS-CoV-2 across age groups and effects of vitamin D. Nasal epithelia were collected from healthy children and adults and cultured for four weeks at air-liquid interface with and without vitamin D. Gene expression (NanoString) and DNA methylation (Illumina EPIC850K) were investigated. Surface protein expression was confirmed by immunofluorescence. Vitamin D receptor (VDR) recruitment was analysed through ChIP. HEp-2 cells were used for protein co-immunoprecipitation and luciferase reporter assays. Compared to children, airway epithelia from adults show higher viral RNA recovery following infection (p<0.01). This was associated with higher ANPEP/CD13 (p<0.001) and reduced type I interferon expression (p<0.01), and differential DNA methylation. In cells from adults, exposure to vitamin D reduced TTLL-12 expression (p=0.01), a negative regulator of interferon expression. This was mediated by VDR recruitment to TTLL12, where it instructs DNA methylation through DNMT1. This study links age-dependant differential expression of CD13 and type I interferon to variable infection of upper airway epithelia. Furthermore, it provides molecular evidence for vitamin D reducing viral replication by inhibiting TTLL-12.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Vitamins, Vitamin D, Interferon Type I, Receptors, Calcitriol, DNA, Adult, Child, COVID-19, SARS-CoV-2 |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 04 Sep 2023 08:48 |
| Last Modified: | 06 Jan 2024 02:10 |
| DOI: | 10.1016/j.mucimm.2023.08.002 |
| Open Access URL: | https://linkinghub.elsevier.com/retrieve/pii/S1933... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3172353 |
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