Immune cell residency in the nasal mucosa may partially explain respiratory disease severity across the age range

Abstract Previous studies focusing on the age disparity in COVID-19 severity have suggested that younger individuals mount a more robust innate immune response in the nasal mucosa after infection with SARS-CoV-2. However, it is unclear if this reflects increased immune activation or increased immune...

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Autores principales:	Konner Winkley, Dithi Banerjee, Todd Bradley, Boryana Koseva, Warren A. Cheung, Rangaraj Selvarangan, Tomi Pastinen, Elin Grundberg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8ee541ee30ab45d29839bf58159db530
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spelling	oai:doaj.org-article:8ee541ee30ab45d29839bf58159db5302021-12-02T18:49:21ZImmune cell residency in the nasal mucosa may partially explain respiratory disease severity across the age range10.1038/s41598-021-95532-32045-2322https://doaj.org/article/8ee541ee30ab45d29839bf58159db5302021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95532-3https://doaj.org/toc/2045-2322Abstract Previous studies focusing on the age disparity in COVID-19 severity have suggested that younger individuals mount a more robust innate immune response in the nasal mucosa after infection with SARS-CoV-2. However, it is unclear if this reflects increased immune activation or increased immune residence in the nasal mucosa. We hypothesized that immune residency in the nasal mucosa of healthy individuals may differ across the age range. We applied single-cell RNA-sequencing and measured the cellular composition and transcriptional profile of the nasal mucosa in 35 SARS-CoV-2 negative children and adults, ranging in age from 4 months to 65 years. We analyzed in total of ~ 30,000 immune and epithelial cells and found that age and immune cell proportion in the nasal mucosa are inversely correlated, with little evidence for structural changes in the transcriptional state of a given cell type across the age range. Orthogonal validation by epigenome sequencing indicate that it is especially cells of the innate immune system that underlie the age-association. Additionally, we characterize the predominate immune cell type in the nasal mucosa: a resident T cell like population with potent antiviral properties. These results demonstrate fundamental changes in the immune cell makeup of the uninfected nasal mucosa over the lifespan. The resource we generate here is an asset for future studies focusing on respiratory infection and immunization strategies.Konner WinkleyDithi BanerjeeTodd BradleyBoryana KosevaWarren A. CheungRangaraj SelvaranganTomi PastinenElin GrundbergNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Konner Winkley Dithi Banerjee Todd Bradley Boryana Koseva Warren A. Cheung Rangaraj Selvarangan Tomi Pastinen Elin Grundberg Immune cell residency in the nasal mucosa may partially explain respiratory disease severity across the age range
description	Abstract Previous studies focusing on the age disparity in COVID-19 severity have suggested that younger individuals mount a more robust innate immune response in the nasal mucosa after infection with SARS-CoV-2. However, it is unclear if this reflects increased immune activation or increased immune residence in the nasal mucosa. We hypothesized that immune residency in the nasal mucosa of healthy individuals may differ across the age range. We applied single-cell RNA-sequencing and measured the cellular composition and transcriptional profile of the nasal mucosa in 35 SARS-CoV-2 negative children and adults, ranging in age from 4 months to 65 years. We analyzed in total of ~ 30,000 immune and epithelial cells and found that age and immune cell proportion in the nasal mucosa are inversely correlated, with little evidence for structural changes in the transcriptional state of a given cell type across the age range. Orthogonal validation by epigenome sequencing indicate that it is especially cells of the innate immune system that underlie the age-association. Additionally, we characterize the predominate immune cell type in the nasal mucosa: a resident T cell like population with potent antiviral properties. These results demonstrate fundamental changes in the immune cell makeup of the uninfected nasal mucosa over the lifespan. The resource we generate here is an asset for future studies focusing on respiratory infection and immunization strategies.
format	article
author	Konner Winkley Dithi Banerjee Todd Bradley Boryana Koseva Warren A. Cheung Rangaraj Selvarangan Tomi Pastinen Elin Grundberg
author_facet	Konner Winkley Dithi Banerjee Todd Bradley Boryana Koseva Warren A. Cheung Rangaraj Selvarangan Tomi Pastinen Elin Grundberg
author_sort	Konner Winkley
title	Immune cell residency in the nasal mucosa may partially explain respiratory disease severity across the age range
title_short	Immune cell residency in the nasal mucosa may partially explain respiratory disease severity across the age range
title_full	Immune cell residency in the nasal mucosa may partially explain respiratory disease severity across the age range
title_fullStr	Immune cell residency in the nasal mucosa may partially explain respiratory disease severity across the age range
title_full_unstemmed	Immune cell residency in the nasal mucosa may partially explain respiratory disease severity across the age range
title_sort	immune cell residency in the nasal mucosa may partially explain respiratory disease severity across the age range
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8ee541ee30ab45d29839bf58159db530
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Immune cell residency in the nasal mucosa may partially explain respiratory disease severity across the age range

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