Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/134285
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Antigen-driven EGR2 expression is required for exhausted CD8⁺ T cell stability and maintenance |
Other Titles: | Antigen-driven EGR2 expression is required for exhausted CD8(+) T cell stability and maintenance |
Author: | Wagle, M.V. Vervoort, S.J. Kelly, M.J. Van Der Byl, W. Peters, T.J. Martin, B.P. Martelotto, L.G. Nüssing, S. Ramsbottom, K.M. Torpy, J.R. Knight, D. Reading, S. Thia, K. Miosge, L.A. Howard, D.R. Gloury, R. Gabriel, S.S. Utzschneider, D.T. Oliaro, J. Powell, J.D. et al. |
Citation: | Nature Communications, 2021; 12(1):1-15 |
Publisher: | Nature Research |
Issue Date: | 2021 |
ISSN: | 2041-1723 2041-1723 |
Statement of Responsibility: | Mayura V. Wagle, Stephin J. Vervoort, Madison J. Kelly, Willem Van Der Byl, Timothy J. Peters, Ben P. Martin ... et al. |
Abstract: | Chronic stimulation of CD8⁺ T cells triggers exhaustion, a distinct differentiation state with diminished effector function. Exhausted cells exist in multiple differentiation states, from stem-like progenitors that are the key mediators of the response to checkpoint blockade, through to terminally exhausted cells. Due to its clinical relevance, there is substantial interest in defining the pathways that control differentiation and maintenance of these subsets. Here, we show that chronic antigen induces the anergy-associated transcription factor EGR2 selectively within progenitor exhausted cells in both chronic LCMV and tumours. EGR2 enables terminal exhaustion and stabilizes the exhausted transcriptional state by both direct EGR2-dependent control of key exhaustion-associated genes, and indirect maintenance of the exhausted epigenetic state. We show that EGR2 is a regulator of exhaustion that epigenetically and transcriptionally maintains the differentiation competency of progenitor exhausted cells. |
Keywords: | CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Animals Mice, Inbred C57BL Mice, Knockout Mice Antigens Lymphopoiesis Clonal Anergy Early Growth Response Protein 2 |
Rights: | © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. |
DOI: | 10.1038/s41467-021-23044-9 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1016953 http://purl.org/au-research/grants/nhmrc/1113904 http://purl.org/au-research/grants/nhmrc/2001719 http://purl.org/au-research/grants/nhmrc/1081858 http://purl.org/au-research/grants/nhmrc/1139607 http://purl.org/au-research/grants/nhmrc/585518 |
Published version: | http://dx.doi.org/10.1038/s41467-021-23044-9 |
Appears in Collections: | Medical Sciences publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
hdl_134285.pdf | Published version | 4.6 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.