{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T22:43:38Z","timestamp":1765233818748,"version":"3.41.2"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T00:00:00Z","timestamp":1721779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Many survivors of preterm birth (&amp;lt;37\u00a0weeks gestation) have lifelong respiratory deficits, the drivers of which remain unknown. Influencers of pathophysiological outcomes are often detectable at the gene level and pinpointing these differences can help guide targeted research and interventions. This study provides the first transcriptomic analysis of primary nasal airway epithelial cells in survivors of preterm birth at approximately 1\u00a0year of age.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Nasal airway epithelial brushings were collected, and primary cell cultures established from term (&amp;gt;37 weeks gestation) and very preterm participants (\u226432 weeks gestation). <jats:italic>Ex vivo<\/jats:italic> RNA was collected from brushings with sufficient cell numbers and <jats:italic>in vitro<\/jats:italic> RNA was extracted from cultured cells, with bulk RNA sequencing performed on both the sample types. Differential gene expression was assessed using the limma-trend pipeline and pathway enrichment identified using Reactome and GO analysis. To corroborate gene expression data, cytokine concentrations were measured in cell culture supernatant.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Transcriptomic analysis to compare term and preterm cells revealed 2,321 genes differentially expressed in <jats:italic>ex vivo<\/jats:italic> samples and 865 genes differentially expressed in cultured basal cell samples. Over one third of differentially expressed genes were related to host immunity, with interferon signalling pathways dominating the pathway enrichment analysis and <jats:italic>IRF1<\/jats:italic> identified as a hub gene. Corroboration of disrupted interferon release showed that concentrations of IFN-\u03b12 were below measurable limits in term samples but elevated in preterm samples [19.4 (76.7) pg\/ml\/\u00b5g protein, <jats:italic>p<\/jats:italic> = 0.03]. IFN-\u03b3 production was significantly higher in preterm samples [3.3 (1.5) vs. 9.4 (17.7) pg\/ml\/\u00b5g protein; <jats:italic>p<\/jats:italic> = 0.01] as was IFN-\u03b2 [7.8 (2.5) vs. 13.6 (19.5) pg\/ml\/\u00b5g protein, <jats:italic>p<\/jats:italic> = 0.01].<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Host immunity may be compromised in the preterm nasal airway epithelium in early life. Altered immune responses may lead to cycles of repeated infections, causing persistent inflammation and tissue damage which can have significant impacts on long-term respiratory function.<\/jats:p>","DOI":"10.3389\/fcell.2024.1399005","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T04:21:47Z","timestamp":1721794907000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomic analysis of primary nasal epithelial cells reveals altered interferon signalling in preterm birth survivors at one year of age"],"prefix":"10.3389","volume":"12","author":[{"given":"Denby J.","family":"Evans","sequence":"first","affiliation":[]},{"given":"Jessica K.","family":"Hillas","sequence":"additional","affiliation":[]},{"given":"Thomas","family":"Iosifidis","sequence":"additional","affiliation":[]},{"given":"Shannon J.","family":"Simpson","sequence":"additional","affiliation":[]},{"given":"Anthony","family":"Kicic","sequence":"additional","affiliation":[]},{"given":"Patricia","family":"Agudelo-Romero","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2024,7,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. 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