TY - JOUR
T1 - Interleukin 2 gene transcription is regulated by Ikaros-induced changes in histone acetylation in anergic T cells
AU - Bandyopadhyay, Sanmay
AU - Duré, Myrianne
AU - Paroder, Monika
AU - Soto-Nieves, Noemí
AU - Puga, Irene
AU - Macián, Fernando
PY - 2007/4/1
Y1 - 2007/4/1
N2 - In T cells anergy may be evoked by an unbalanced stimulation of the T-cell receptor in the absence of costimulation. Anergic T cells are unresponsive to new antigen receptor engagement and do not produce interleukin 2. We present evidence that anergizing stimuli induce changes in histone acetylation, which mediates transcriptional repression of interleukin 2 expression. In response to calcium signaling, anergic T cells up-regulate the expression of Ikaros, a zinc finger transcription factor essential for lymphoid lineage determination. Ikaros binds to the interleukin 2 promoter where it induces histone deacetylation. Confirming the role of Ikaros in the induction of T-cell anergy, cells with reduced Ikaros activity show defective inactivation in response to an anergizing stimulus. We propose a model in which tolerizing stimuli induce epigenetic changes on the interleukin 2 locus that are responsible for the stable inhibition of the expression of this cytokine in anergic T cells.
AB - In T cells anergy may be evoked by an unbalanced stimulation of the T-cell receptor in the absence of costimulation. Anergic T cells are unresponsive to new antigen receptor engagement and do not produce interleukin 2. We present evidence that anergizing stimuli induce changes in histone acetylation, which mediates transcriptional repression of interleukin 2 expression. In response to calcium signaling, anergic T cells up-regulate the expression of Ikaros, a zinc finger transcription factor essential for lymphoid lineage determination. Ikaros binds to the interleukin 2 promoter where it induces histone deacetylation. Confirming the role of Ikaros in the induction of T-cell anergy, cells with reduced Ikaros activity show defective inactivation in response to an anergizing stimulus. We propose a model in which tolerizing stimuli induce epigenetic changes on the interleukin 2 locus that are responsible for the stable inhibition of the expression of this cytokine in anergic T cells.
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U2 - 10.1182/blood-2006-07-037754
DO - 10.1182/blood-2006-07-037754
M3 - Article
C2 - 17148585
AN - SCOPUS:33947611357
SN - 0006-4971
VL - 109
SP - 2878
EP - 2886
JO - Blood
JF - Blood
IS - 7
ER -