CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response

Marc Martínez-Llordella, Jonathan H. Esensten, Samantha L. Bailey-Bucktrout, Robert H. Lipsky, Ann Marini, Jun Chen, Mohamed Mughal, Mark P. Mattson, Dennis D. Taub, Jeffrey A. Bluestone

Research output: Contribution to journalArticlepeer-review

Abstract

During the initial hours after activation, CD4+ T cells experience profound changes in gene expression. Co-stimulation via the CD28 receptor is required for efficient activation of naive T cells. However, the transcriptional consequences of CD28 co-stimulation are not completely understood. We performed expression microarray analysis to elucidate the effectsof CD28 signals on the transcriptome of activated T cells. We show that the transcription factor DEC1 is highly induced in a CD28-dependent manner upon T cell activation, is involved in essential CD4+ effector T cell functions, and participates in the transcriptional regulation of several T cell activation pathways, including a large group of CD28-regulated genes. Antigen-specific, DEC1-deficient CD4+ T cells have cell-intrinsic defects in survival and proliferation. Furthermore, we found that DEC1 is required for the development of experimental autoimmune encephalomyelitis because of its critical role in the production of the proinflammatory cytokines GM-CSF, IFN-γ, and IL-2. Thus, we identify DEC1 as a critical transcriptional mediator in the activation of naive CD4+ T cells that is required for the development of a T cell-mediated autoimmune disease.

Original languageEnglish (US)
Pages (from-to)1603-1619
Number of pages17
JournalJournal of Experimental Medicine
Volume210
Issue number8
DOIs
StatePublished - 2013
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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