000			02811 am a22003133u 4500
042			_adc
100	1	0	_aElliot, Thomas A. E. _eauthor _92099
700	1	0	_aJennings, Emma K. _eauthor _92100
700	1	0	_aLecky, David A. J. _eauthor _92101
700	1	0	_aRouvray, Sophie _eauthor _92102
700	1	0	_aMackie, Gillian M. _eauthor _92103
700	1	0	_aScarfe, Lisa _eauthor _92104
700	1	0	_aSheriff, Lozan _eauthor _92105
700	1	0	_aOno, Masahiro _eauthor _92106
700	1	0	_aMaslowski, Kendle M. _eauthor _92107
700	1	0	_aBending, David _eauthor _92108
245	0	0	_aNur77-Tempo mice reveal T cell steady state antigen recognition
260			_c2022-12-22.
500			_a/pmc/articles/PMC7614040/
500			_a/pubmed/36704407
520			_aIn 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.
540			_a
540			_ahttps://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.
546			_aen
690			_aArticle
655	7		_aText _2local
786	0		_nDiscov Immunol
856	4	1	_uhttp://dx.doi.org/10.1093/discim/kyac009 _zConnect to this object online.
999			_c875 _d875