GSE49366
EGR2 is Critical for Peripheral Naïve T Cell Differentiation and the T-cell Response to Influenza
EGR2 is an early growth response transcription factor that negatively regulates T-cell activation, in contrast to its positive regulation by EGR1. Here, we unexpectedly found that EGR2 promotes peripheral naïve T cell differentiation, with delayed TCR-induced proliferation in naïve T cells from Egr2 conditional knockout (CKO) mice, and decreased production of IFN-?, 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 and infiltration of antigen-specific memory-precursor CD8+ T cells but lower numbers of lung-resident memory CD8+ T cells. Thus unexpectedly EGR2 can function as a positive regulator that is essential for naïve T-cell differentiation and in vivo T-cell responses to a viral infection. Overall design: Genome-wide transcription factors mapping and binding of EGR2 in mouse Total T cells. RNA-Seq is conducted in WT and Egr2-/- mice.