Nr4a1 and Nr4a3 reporter mice are differentially sensitive to T cell receptor signal strength and duration.
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Nr4a receptors are activated by T cell receptor (TCR) signaling and play key roles in T cell differentiation. Which TCR signaling pathways regulate Nr4a receptors and their sensitivities to TCR signal strength and duration remains unclear. Using Nr4a1/Nur77-GFP and Nr4a3-Timer of cell kinetics and activity (Tocky) mice, we elucidate the signaling pathways governing Nr4a receptor expression. We reveal that Nr4a1-Nr4a3 are Src family kinase dependent. Moreover, Nr4a2 and Nr4a3 are attenuated by calcineurin inhibitors and bind nuclear factor of activated T cells 1 (NFAT1), highlighting a necessary and sufficient role for NFAT1 in the control of Nr4a2 and Nr4a3, but redundancy for Nr4a1. Nr4a1-GFP is activated by tonic and cognate signals during T cell development, whereas Nr4a3-Tocky requires cognate peptide:major histocompatibility complex (MHC) interactions for expression. Compared to Nr4a3-Tocky, Nr4a1-GFP is approximately 2- to 3-fold more sensitive to TCR signaling and is detectable by shorter periods of TCR signaling. These findings suggest that TCR signal duration may be an underappreciated aspect influencing the developmental fate of T cells in vivo.
Date Issued
2020-11-03
Date Acceptance
2020-10-08
Citation
Cell Research, 2020, 33 (5), pp.1-15
ISSN
1001-0602
Publisher
Shanghai Institutes for Biological Sciences
Start Page
1
End Page
15
Journal / Book Title
Cell Research
Volume
33
Issue
5
Copyright Statement
© 2020 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Sponsor
Biotechnology and Biological Sciences Research Council
Biotechnology and Biological Sciences Research Council (BBSRC)
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33147449
PII: S2211-1247(20)31317-6
Grant Number
BB/J013951/1
BB/J013951/2
Subjects
NFAT
Nr4a1-GFP
Nr4a3-Tocky
T cell activation
T cell development
T cell receptor signaling
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2020-11-03