title: Transcriptional regulator early growth response gene 2 (Egr2) is required for T cell anergy in vitro and in vivo.
abstract: T cell receptor engagement in the absence of costimulation results in a hyporesponsive state termed anergy. Understanding the transcriptional regulation of other T cell differentiation states has provided critical information regarding the biology of T cell regulation in vivo. However, the transcriptional regulation of T cell anergy has been poorly understood. Using the key anergy target gene diacylglycerol kinase (DGK) α as a focal point, we identified early growth response gene 2 (Egr2) as a central transcription factor that regulates the anergic state. Conditional Egr2 deletion in peripheral T cells abolishes induced expression of DGK-α and other anergy genes and restores Ras/MAPK signaling, IL-2 production, and proliferation upon attempted anergy induction. Using superantigen- and tumor-induced anergy models, we found that Egr2 is necessary for anergy induction in vivo. Collectively, our results implicate Egr2 as an essential transcriptional regulator of the T cell anergy program.
authors.affiliation: Department of Pathology and 2 Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zha
authors.forename: Gregory
authors.initials: G
authors.lastname: Driessens
authors.forename: Frederick
authors.initials: F
authors.lastname: Locke
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D017635:Clonal Anergy / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D019852:Diacylglycerol Kinase / Q000235:genetics / Q000378:metabolism*; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D008156:Luciferases; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D017931:DNA Primers; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D008156:Luciferases; D019852:Diacylglycerol Kinase