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

First Author  Martínez-Llordella M Year  2013
Journal  J Exp Med Volume  210
Issue  8 Pages  1603-19
PubMed ID  23878307 Mgi Jnum  J:202364
Mgi Id  MGI:5518528 Doi  10.1084/jem.20122387
Citation  Martinez-Llordella M, et al. (2013) CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response. J Exp Med 210(8):1603-19
abstractText  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 effects of 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-gamma, 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.
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