JOM KITA KE POLITEKNIK

Nur77-Tempo mice reveal T cell steady state antigen recognition (Record no. 2160)

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Authentication code dc
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Personal name Elliot, Thomas A. E.
Relator term author
9 (RLIN) 2099
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Title Nur77-Tempo mice reveal T cell steady state antigen recognition
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Date of publication, distribution, etc. 2022-12-22.
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General note /pmc/articles/PMC7614040/
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General note /pubmed/36704407
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Summary, etc. In lymphocytes, Nr4a gene expression is specifically regulated by antigen receptor signalling, making them ideal targets for use as distal T cell receptor (TCR) reporters. Nr4a3-Timer of cell kinetics and activity (Tocky) mice are a ground-breaking tool to report TCR-driven Nr4a3 expression using Fluorescent Timer protein (FT). FT undergoes a time-dependent shift in its emission spectrum following translation, allowing for the temporal reporting of transcriptional events. Our recent work suggested that Nr4a1/Nur77 may be a more sensitive gene to distal TCR signals compared to Nr4a3, so we, therefore, generated Nur77-Timer-rapidly-expressed-in-lymphocytes (Tempo) mice that express FT under the regulation of Nur77. We validated the ability of Nur77-Tempo mice to report TCR and B cell receptor signals and investigated the signals regulating Nur77-FT expression. We found that Nur77-FT was sensitive to low-strength TCR signals, and its brightness was graded in response to TCR signal strength. Nur77-FT detected positive selection signals in the thymus, and analysis of FT expression revealed that positive selection signals are often persistent in nature, with most thymic Treg expressing FT Blue. We found that active TCR signals in the spleen are low frequency, but CD69(+) lymphoid T cells are enriched for FT Blue(+) Red(+) T cells, suggesting frequent TCR signalling. In non-lymphoid tissue, we saw a dissociation of FT protein from CD69 expression, indicating that tissue residency is not associated with tonic TCR signals. Nur77-Tempo mice, therefore, combine the temporal dynamics from the Tocky innovation with increased sensitivity of Nr4a1 to lower TCR signal strengths.
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Terms governing use and reproduction
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Terms governing use and reproduction https://creativecommons.org/licenses/by/4.0/This work is licensed under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) International license.
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Language note en
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Topical term or geographic name as entry element Article
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Genre/form data or focus term Text
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Personal name Jennings, Emma K.
Relator term author
9 (RLIN) 2100
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Personal name Lecky, David A. J.
Relator term author
9 (RLIN) 2101
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Personal name Rouvray, Sophie
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9 (RLIN) 2102
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Personal name Mackie, Gillian M.
Relator term author
9 (RLIN) 2103
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Personal name Scarfe, Lisa
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9 (RLIN) 2104
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Personal name Sheriff, Lozan
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9 (RLIN) 2105
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Personal name Ono, Masahiro
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9 (RLIN) 2106
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Personal name Maslowski, Kendle M.
Relator term author
9 (RLIN) 2107
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Personal name Bending, David
Relator term author
9 (RLIN) 2108
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Note Discov Immunol
856 41 - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="http://dx.doi.org/10.1093/discim/kyac009">http://dx.doi.org/10.1093/discim/kyac009</a>
Public note Connect to this object online.

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