Imperial College London
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DrMasahiroOno

Faculty of Natural Sciences, Department of Life Sciences

Reader in Immunology
 
 
 
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Contact

 

m.ono

 
 
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Location

 

605Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Jennings:2019:10.1101/767566,
author = {Jennings, E and Elliot, TAE and Thawait, N and Kanabar, S and Yam-Puc, JC and Ono, M and Toellner, K-M and Wraith, DC and Anderson, G and Bending, D},
doi = {10.1101/767566},
title = {Differential Nr4a1 and Nr4a3 expression discriminates tonic from activated TCR signalling events in vivo},
url = {http://dx.doi.org/10.1101/767566},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Summary</jats:title><jats:p><jats:italic>Nr4a</jats:italic>receptors are activated by T cell receptor (TCR) and B cell receptor (BCR) signalling and play key roles in T cell differentiation and promoting T cell exhaustion. How TCR signalling pathways regulate Nr4a receptors and their sensitivities to different physiological types of TCR signalling (e.g. tonic versus activating) remains unknown. Here we utilise Nr4a1/Nur77-GFP and<jats:italic>Nr4a3</jats:italic>-Tocky mice to elucidate the signalling pathways that govern Nr4a receptor expression in CD4<jats:sup>+</jats:sup>and CD8<jats:sup>+</jats:sup>T cells. Our findings reveal that<jats:italic>Nr4a1-3</jats:italic>are Src family kinase-dependent. Moreover,<jats:italic>Nr4a2</jats:italic>and<jats:italic>Nr4a3</jats:italic>are abolished by calcineurin inhibitors and bind NFAT1, highlighting a necessary and sufficient role for NFAT in the control of<jats:italic>Nr4a2</jats:italic>and<jats:italic>Nr4a3</jats:italic>, but redundancy for NFAT for<jats:italic>Nr4a1</jats:italic>. During T cell development, Nr4a1 is activated by tonic signalling during TCR-beta selection in the thymus, whilst Nr4a3 requires cognate peptide:MHC interactions for expression. Thus, due to differential sensitivity of Nr4a1 and Nr4a3 to TCR signalling pathways, T cells undergoing tonic versus activating TCR signalling events can be distinguished in vivo.</jats:p>
AU  - Jennings,E
AU  - Elliot,TAE
AU  - Thawait,N
AU  - Kanabar,S
AU  - Yam-Puc,JC
AU  - Ono,M
AU  - Toellner,K-M
AU  - Wraith,DC
AU  - Anderson,G
AU  - Bending,D
DO  - 10.1101/767566
PY  - 2019///
TI  - Differential Nr4a1 and Nr4a3 expression discriminates tonic from activated TCR signalling events in vivo
UR  - http://dx.doi.org/10.1101/767566
ER  -
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