TY - JOUR
T1 - CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response
AU - Martínez-Llordella, Marc
AU - Esensten, Jonathan H.
AU - Bailey-Bucktrout, Samantha L.
AU - Lipsky, Robert H.
AU - Marini, Ann
AU - Chen, Jun
AU - Mughal, Mohamed
AU - Mattson, Mark P.
AU - Taub, Dennis D.
AU - Bluestone, Jeffrey A.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20122387
DO - 10.1084/jem.20122387
M3 - Article
C2 - 23878307
AN - SCOPUS:84884230330
SN - 0022-1007
VL - 210
SP - 1603
EP - 1619
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 8
ER -