TY - JOUR
T1 - EGR2 is critical for peripheral naíve T-cell differentiation and the T-cell response to influenza
AU - Du, Ning
AU - Kwon, Hyokjoon
AU - Li, Peng
AU - West, Erin E.
AU - Oh, Jangsuk
AU - Liao, Wei
AU - Yu, Zuxi
AU - Ren, Min
AU - Leonard, Warren J.
PY - 2014/11/18
Y1 - 2014/11/18
N2 - 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.
AB - 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.
KW - Differentiation
KW - EGR2
KW - Influenza
KW - RNA-Seq
KW - T cells
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UR - http://www.scopus.com/inward/citedby.url?scp=84919494506&partnerID=8YFLogxK
U2 - 10.1073/pnas.1417215111
DO - 10.1073/pnas.1417215111
M3 - Article
C2 - 25368162
AN - SCOPUS:84919494506
SN - 0027-8424
VL - 111
SP - 16484
EP - 16489
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 46
M1 - A65
ER -