Age-differential CD13 and interferon expression in airway epithelia affect SARS-CoV-2 infection - Effects of vitamin D

Sposito, Francesca, Pennington, Shaun ORCID: https://orcid.org/0000-0002-7160-6275, David, Christopher A.W., Duggan, Jack, Northey, Sarah, Biagini, Giancarlo ORCID: https://orcid.org/0000-0001-6356-6595, Liptrott, Neill J., Charras, Amandine, McNamara, Paul S. and Hedrich, Christian M. (2023) 'Age-differential CD13 and interferon expression in airway epithelia affect SARS-CoV-2 infection - Effects of vitamin D'. Mucosal Immunology, Vol 16, Issue 6, pp. 776-787.

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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 the air-liquid interface with and without vitamin D. Gene expression and DNA methylation were investigated. Surface protein expression was confirmed by immunofluorescence while vitamin D receptor recruitment to the DNA was analysed through chromatin immunoprecipitation. 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. This was associated with higher ANPEP/CD13, reduced type I interferon expression, and differential DNA methylation. In cells from adults, exposure to vitamin D reduced TTLL-12 expression, a negative regulator of the interferon response. This was mediated by vitamin D receptor recruitment to TTLL12, where it instructs DNA methylation through DNA methyltransferase 1.
This study links age-dependent 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
Subjects:	QU Biochemistry > Vitamins > QU 160 Vitamins. Vitamin requirements WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 506 COVID-19
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.mucimm.2023.08.002
Depositing User:	Clare O'Neill
Date Deposited:	12 Sep 2023 10:41
Last Modified:	03 Dec 2024 10:48
URI:	https://archive.lstmed.ac.uk/id/eprint/23106

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