Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/107233
DC Field | Value | Language |
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dc.contributor.author | Mold, Jeff E | - |
dc.contributor.author | Réu, Pedro | - |
dc.contributor.author | Olin, Axel | - |
dc.contributor.author | Bernard, Samuel | - |
dc.contributor.author | Michaëlsson, Jakob | - |
dc.contributor.author | Rane, Sanket | - |
dc.contributor.author | Yates, Andrew | - |
dc.contributor.author | Khosravi, Azadeh | - |
dc.contributor.author | Salehpour, Mehran | - |
dc.contributor.author | Possnert, Göran | - |
dc.contributor.author | Brodin, Petter | - |
dc.contributor.author | Frisén, Jonas | - |
dc.date.accessioned | 2023-06-15T11:08:06Z | - |
dc.date.available | 2023-06-15T11:08:06Z | - |
dc.date.issued | 2019-10 | - |
dc.identifier.issn | 1545-7885 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/107233 | - |
dc.description.abstract | Thymic involution and proliferation of naive T cells both contribute to shaping the naive T-cell repertoire as humans age, but a clear understanding of the roles of each throughout a human life span has been difficult to determine. By measuring nuclear bomb test-derived 14C in genomic DNA, we determined the turnover rates of CD4+ and CD8+ naive T-cell populations and defined their dynamics in healthy individuals ranging from 20 to 65 years of age. We demonstrate that naive T-cell generation decreases with age because of a combination of declining peripheral division and thymic production during adulthood. Concomitant decline in T-cell loss compensates for decreased generation rates. We investigated putative mechanisms underlying age-related changes in homeostatic regulation of CD4+ naive T-cell turnover, using mass cytometry to profile candidate signaling pathways involved in T-cell activation and proliferation relative to CD31 expression, a marker of thymic proximity for the CD4+ naive T-cell population. We show that basal nuclear factor κB (NF-κB) phosphorylation positively correlated with CD31 expression and thus is decreased in peripherally expanded naive T-cell clones. Functionally, we found that NF-κB signaling was essential for naive T-cell proliferation to the homeostatic growth factor interleukin (IL)-7, and reduced NF-κB phosphorylation in CD4+CD31- naive T cells is linked to reduced homeostatic proliferation potential. Our results reveal an age-related decline in naive T-cell turnover as a putative regulator of naive T-cell diversity and identify a molecular pathway that restricts proliferation of peripherally expanded naive T-cell clones that accumulate with age. | pt |
dc.description.sponsorship | This work was supported by grants from the Swedish Research Council (https://www.vr.se/english.html; D0761801 to JF), Swedish Cancer Society (https://www.cancerfonden.se/omcancerfonden/ about-the-swedish-cancer-society; CAN 2016/505 to JF), Strategic Research Programme in Stem Cells and Regenerative Medicine (StratRegen) (https://ki.se/en/research/ stratregen-research; to JF), Knut och Alice Wallenbergs Stiftelse (https://kaw.wallenberg.org; KAW 2018.0063), Torsten So¨derbergs Stiftelse (professorship to JF), Portuguese Foundation for Science and Technology (https://www.fct.pt/fct. phtml.en; SFRH/BD/33465/2008 to PR), Human Frontiers Long-Term Fellowship (http://www.hfsp. org; LT-000231/2011-L to JEM), Swedish Society for Medicine (https://www.ssmf.se/about-ssmf-inenglish/; SLS505921 to PB). | pt |
dc.language.iso | eng | pt |
dc.publisher | Public Library of Science | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject.mesh | Adult | pt |
dc.subject.mesh | Aged | pt |
dc.subject.mesh | Aging | pt |
dc.subject.mesh | CD4-Positive T-Lymphocytes | pt |
dc.subject.mesh | CD8-Positive T-Lymphocytes | pt |
dc.subject.mesh | Cell Lineage | pt |
dc.subject.mesh | Cell Proliferation | pt |
dc.subject.mesh | Female | pt |
dc.subject.mesh | Gene Expression Regulation, Developmental | pt |
dc.subject.mesh | Homeostasis | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Immunophenotyping | pt |
dc.subject.mesh | Interleukin-7 | pt |
dc.subject.mesh | Lymphocyte Activation | pt |
dc.subject.mesh | Male | pt |
dc.subject.mesh | Middle Aged | pt |
dc.subject.mesh | NF-kappa B | pt |
dc.subject.mesh | Phosphorylation | pt |
dc.subject.mesh | Platelet Endothelial Cell Adhesion Molecule-1 | pt |
dc.subject.mesh | Signal Transduction | pt |
dc.subject.mesh | Thymus Gland | pt |
dc.title | Cell generation dynamics underlying naive T-cell homeostasis in adult humans | pt |
dc.type | article | - |
degois.publication.firstPage | e3000383 | pt |
degois.publication.issue | 10 | pt |
degois.publication.title | PLoS Biology | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1371/journal.pbio.3000383 | pt |
degois.publication.volume | 17 | pt |
dc.date.embargo | 2019-10-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.grantfulltext | open | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
item.openairetype | article | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
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Cell-generation-dynamics-underlying-naive-Tcell-homeostasis-in-adult-humansPLoS-Biology.pdf | 3.27 MB | Adobe PDF | View/Open |
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