Transcriptional Regulator Early Growth Response Gene 2 (Egr2) is Required for T Cell Anergy in Vitro and in Vivo

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2012 Nov 7

PMID 23129747

Citations 66

Authors

Yan Zheng

Yuanyuan Zha

Gregory Driessens

Frederick Locke

Thomas F Gajewski

Affiliations

Soon will be listed here.

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.

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