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Cutting Edge: TCR-Induced NAB2 Enhances T Cell Function by Coactivating IL-2 Transcription¹

Samuel Collins^*, Lawrence A. Wolfraim, Charles G. Drake^*, Maureen R. Horton and Jonathan D. Powell^2,*

^* Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231; MaxCyte, Inc., Gaithersburg, MD 20878; and Division of Pulmonary Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231

TCR engagement leads to the up-regulation of genetic programs that can both activate and inhibit T cell function. The early growth receptor (Egr) proteins Egr-2 and Egr-3 have recently been identified as TCR-induced negative regulators of T cell function. NAB2 (NGFI-A-binding protein 2) is both a coactivator and a corepressor of Egr-mediated transcription and has been implicated in regulating Schwann cell myelination. In this report we demonstrate that NAB2 is induced by TCR engagement and that its expression is enhanced by the presence of costimulation. The overexpression of NAB2 enhanced IL-2 production while small interfering RNA to NAB2 markedly inhibited IL-2 expression. Mechanistically, we demonstrate that NAB2 enhances IL-2 transcription by acting as a coactivator for Egr-1. Indeed, chromatin immunoprecipitation analysis reveals that NAB2 is recruited to the Egr-1 binding site of the IL-2 promoter. Taken together, our findings identify NAB2 as a novel coactivator of T cell function.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was funded by National Institutes of Health Grant R01CA098109.

² Address correspondence and reprint requests to Dr. Jonathan D. Powell, Cancer Research Building I, Room 443, 1650 Orleans Street, Baltimore, MD 21231. E-mail address: poweljo{at}jhmi.edu

³ Abbreviations used in this paper: Egr, early growth response; ChIP, chromatin immunoprecipitation; CSA, cyclosporin A; DNNAB2, dominant negative NAB2; siRNA, small interfering RNA.