Pluto Biosciences, Inc

GSE49366: EGR2 is Critical for Peripheral Nave T cell Differentiation and the T-Cell Mediated Response to Influenza

Bulk RNA sequencing

EGR1 and EGR2 are closely related members of an early growth response family of transcription factors, with EGR1 generally considered to be a positive regulator and EGR2 a negative regulator of T cell activation, promoting T cell anergy while decreasing autoimmunity. Here, we unexpectedly found that EGR2, but not EGR1, acted as a positive regulator of peripheral nave T cell differentiation and T cell-mediated immune responses. Deletion of the Egr2 gene delayed TCR-induced proliferation of peripheral nave CD4+ and CD8+ T cells more than deletion of the Egr1 gene, with reduced expression of IL-2 and IL-2R in primary stimulated CD4+ T cells, lower proliferation than Egr1-deficient T cells and lower IFN-, IL-4, IL-9, and IL-17A expression under Th1, Th2, Th9, and Th17 differentiation conditions, respectively. Consistent with this, a group of genes including Tbx21 and Notch1, which positively regulate T cell activation and proliferation, bound EGR2 and were down-regulated in Egr2 CKO T cells. Moreover, EGR2 was necessary for T cell-mediated immune responses to influenza infection, with delayed virus clearance, greater weight loss, and more severe pathologic changes in Egr2 conditional KO (CKO) mice than in WT or Egr1 KO mice. Furthermore, Egr2 CKO mice had dysregulated cytokine expression and infiltration of antigen-specific CD8+ T cells that had a memory precursor phenotype and decreased cytolytic activity. Collectively, these results unexpectedly reveal that EGR2 is an essential transcriptional regulator for the differentiation of nave T cells and a critical positive regulator of the T cell immune response to influenza infection. SOURCE: Peng Li (peng.li@nih.gov) - LMI NIH

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