Early programming of CD8+ T cell response by the orphan nuclear receptor NR4A3

Enhancing long-term persistence while simultaneously potentiating the effector response of CD8+ T cells has been a long-standing goal in immunology to produce better vaccines and adoptive cell therapy products. NR4A3 is a transcription factor of the orphan nuclear receptor family. While it is rapidly and transiently expressed following T cell activation, its role in the early stages of T cell response is unknown. We show that NR4A3-deficient murine CD8+ T cells differentiate preferentially into memory precursor and central memory cells, but also produce more cytokines. This is explained by an early influence of NR4A3 deficiency on the memory transcriptional program and on accessibility of chromatin regions with motifs for bZIP transcription factors, which impacts the transcription of Fos/Jun target genes. Our results reveal a unique and early role for NR4A3 in programming CD8+ T cell differentiation and function. Manipulating NR4A3 activity may represent a promising strategy to improve vaccination and T cell therapy.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:117

Enthalten in:

Proceedings of the National Academy of Sciences of the United States of America - 117(2020), 39 vom: 29. Sept., Seite 24392-24402

Sprache:

Englisch

Beteiligte Personen:

Odagiu, Livia [VerfasserIn]
Boulet, Salix [VerfasserIn]
Maurice De Sousa, Dave [VerfasserIn]
Daudelin, Jean-François [VerfasserIn]
Nicolas, Sandrine [VerfasserIn]
Labrecque, Nathalie [VerfasserIn]

Links:

Volltext

Themen:

DNA-Binding Proteins
Early CD8+ T cell response
Journal Article
NR4A3
Nerve Tissue Proteins
Nr4a3 protein, mouse
Nuclear receptors
Receptors, Steroid
Receptors, Thyroid Hormone
Research Support, Non-U.S. Gov't
T cell function
T cell memory
Transcription Factors

Anmerkungen:

Date Completed 18.12.2020

Date Revised 10.03.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1073/pnas.2007224117

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM314852468