tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A. 2014 Nov 3. pii: 201417215. [Epub ahead of print]
EGR2 is critical for peripheral na?ve T-cell differentiation and the T-cell response to influenza.
Du N1, Kwon H1, Li P1, West EE1, Oh J1, Liao W1, Yu Z2, Ren M1, Leonard WJ3.
Author information
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 na?ve T-cell differentiation, with delayed T-cell receptor-induced proliferation in na?ve 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 na?ve T-cell differentiation and in vivo T-cell responses to a viral infection.
KEYWORDS:
EGR2; RNA-Seq; T cells; differentiation; influenza
PMID:
25368162
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25368162
EGR2 is critical for peripheral na?ve T-cell differentiation and the T-cell response to influenza.
Du N1, Kwon H1, Li P1, West EE1, Oh J1, Liao W1, Yu Z2, Ren M1, Leonard WJ3.
Author information
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 na?ve T-cell differentiation, with delayed T-cell receptor-induced proliferation in na?ve 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 na?ve T-cell differentiation and in vivo T-cell responses to a viral infection.
KEYWORDS:
EGR2; RNA-Seq; T cells; differentiation; influenza
PMID:
25368162
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25368162