title: EGR2 is critical for peripheral naïve T-cell differentiation and the T-cell response to influenza.
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 naïve T-cell differentiation, with delayed T-cell receptor-induced proliferation in naïve 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 naïve T-cell differentiation and in vivo T-cell responses to a viral infection.
authors.affiliation: Laboratory of Molecular Immunology and Immunology Center, and.
authors.forename: Ning
authors.initials: N
authors.lastname: Du
authors.affiliation: Laboratory of Molecular Immunology and Immunology Center, and.
authors.forename: Hyokjoon
authors.initials: H
authors.lastname: Kwon
authors.affiliation: Laboratory of Molecular Immunology and Immunology Center, and.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Immunology and Immunology Center, and.
authors.forename: Erin E
authors.initials: EE
authors.lastname: West
authors.affiliation: Laboratory of Molecular Immunology and Immunology Center, and.
authors.forename: Jangsuk
authors.initials: J
authors.lastname: Oh
authors.affiliation: Laboratory of Molecular Immunology and Immunology Center, and.
authors.forename: Wei
authors.initials: W
authors.lastname: Liao
authors.affiliation: Pathology Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1674.
authors.forename: Zuxi
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Laboratory of Molecular Immunology and Immunology Center, and.
authors.forename: Min
authors.initials: M
authors.lastname: Ren
authors.affiliation: Laboratory of Molecular Immunology and Immunology Center, and wjl@helix.nih.gov.
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D051766:Early Growth Response Protein 1 / Q000502:physiology; D051767:Early Growth Response Protein 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D007156:Immunologic Memory; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000302:isolation & purification; D008168:Lung / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D038041:Lymphopoiesis / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051881:Receptor, Notch1 / Q000096:biosynthesis / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D019562:Viral Load; D000098815:T-bet Transcription Factor
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; C486109:Egr1 protein, mouse; C497327:Egr2 protein, mouse; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011948:Receptors, Antigen, T-Cell; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor
keywords: EGR2; RNA-Seq; T cells; differentiation; influenza