EGR2 is critical for peripheral naíve T-cell differentiation and the T-cell response to influenza

Ning Du, Hyokjoon Kwon, Peng Li, Erin E. West, Jangsuk Oh, Wei Liao, Zuxi Yu, Min Ren, Warren J. Leonard

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Early growth response 2 (EGR2) transcription factor negatively regulates T-cell activation, in contrast to the positive regulation of this process by EGR1. Here, we unexpectedly found that EGR2 promotes peripheral naive T-cell differentiation, with delayed T-cell receptor-induced proliferation in naive T cells from Egr2 conditional knockout (CKO) mice and decreased production of IFN-γ, IL-4, IL-9, and IL-17A in cells subjected to T-helper differentiation. Moreover, genes that promote T-cell activation, including Tbx21 and Notch1, had decreased expression in Egr2 CKO T cells and are direct EGR2 target genes. Following influenza infection, Egr2 CKO mice had delayed viral clearance, more weight loss, and more severe pathological changes in the lung than did WT and Egr1 KO mice, with decreased production of effector cytokines, increased infiltration of antigen-specific memory-precursor CD8+ T cells, and lower numbers of lung-resident memory CD8+ T cells. Thus, unexpectedly, EGR2 can function as a positive regulator that is essential for naive T-cell differentiation and in vivo T-cell responses to a viral infection.

Original languageEnglish (US)
Article numberA65
Pages (from-to)16484-16489
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number46
DOIs
StatePublished - Nov 18 2014

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Human Influenza
Cell Differentiation
T-Lymphocytes
Growth
Knockout Mice
Early Growth Response Transcription Factors
Interleukin-9
Lung
Interleukin-17
Virus Diseases
T-Cell Antigen Receptor
Interleukin-4
Genes
Weight Loss
Cell Count
Cytokines
Antigens
Infection

Keywords

  • Differentiation
  • EGR2
  • Influenza
  • RNA-Seq
  • T cells

ASJC Scopus subject areas

  • General

Cite this

EGR2 is critical for peripheral naíve T-cell differentiation and the T-cell response to influenza. / Du, Ning; Kwon, Hyokjoon; Li, Peng; West, Erin E.; Oh, Jangsuk; Liao, Wei; Yu, Zuxi; Ren, Min; Leonard, Warren J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 46, A65, 18.11.2014, p. 16484-16489.

Research output: Contribution to journalArticle

Du, Ning ; Kwon, Hyokjoon ; Li, Peng ; West, Erin E. ; Oh, Jangsuk ; Liao, Wei ; Yu, Zuxi ; Ren, Min ; Leonard, Warren J. / EGR2 is critical for peripheral naíve T-cell differentiation and the T-cell response to influenza. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 46. pp. 16484-16489.
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