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Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs
被引:366
作者:

Cruz-Guilloty, Fernando
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机构:
Harvard Univ, Sch Med, Boston, MA 02115 USA
Immune Dis Inst, Boston, MA 02115 USA Harvard Univ, Sch Med, Boston, MA 02115 USA

Pipkin, Matthew E.
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h-index: 0
机构:
Harvard Univ, Sch Med, Boston, MA 02115 USA
Immune Dis Inst, Boston, MA 02115 USA Harvard Univ, Sch Med, Boston, MA 02115 USA

Djuretic, Ivana M.
论文数: 0 引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Boston, MA 02115 USA
Immune Dis Inst, Boston, MA 02115 USA Harvard Univ, Sch Med, Boston, MA 02115 USA

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Lotem, Joseph
论文数: 0 引用数: 0
h-index: 0
机构:
Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel Harvard Univ, Sch Med, Boston, MA 02115 USA

Lichtenheld, Mathias G.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Miami, Dept Microbiol & Immunol, Sylvester Comprehens Canc Ctr, Miller Sch Med, Miami, FL USA Harvard Univ, Sch Med, Boston, MA 02115 USA

Groner, Yoram
论文数: 0 引用数: 0
h-index: 0
机构:
Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel Harvard Univ, Sch Med, Boston, MA 02115 USA

Rao, Anjana
论文数: 0 引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Boston, MA 02115 USA
Immune Dis Inst, Boston, MA 02115 USA Harvard Univ, Sch Med, Boston, MA 02115 USA
机构:
[1] Harvard Univ, Sch Med, Boston, MA 02115 USA
[2] Immune Dis Inst, Boston, MA 02115 USA
[3] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel
[4] Univ Miami, Dept Microbiol & Immunol, Sylvester Comprehens Canc Ctr, Miller Sch Med, Miami, FL USA
关键词:
HELPER TYPE-1 CELLS;
IL4;
SILENCER;
BET;
PERFORIN;
DIFFERENTIATION;
EOMESODERMIN;
MEMORY;
REPRESSION;
HOMEOSTASIS;
ACTIVATION;
D O I:
10.1084/jem.20081242
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Activation of naive CD8(+) T cells with antigen induces their differentiation into effector cytolytic T lymphocytes (CTLs). CTLs lyse infected or aberrant target cells by exocytosis of lytic granules containing the pore-forming protein perforin and a family of proteases termed granzymes. We show that effector CTL differentiation occurs in two sequential phases in vitro, characterized by early induction of T-bet and late induction of Eomesodermin (Eomes), T-box transcription factors that regulate the early and late phases of interferon (IFN) gamma expression, respectively. In addition, we demonstrate a critical role for the transcription factor Runx3 in CTL differentiation. Runx3 regulates Eomes expression as well as expression of three cardinal markers of the effector CTL program: IFN-gamma, perforin, and granzyme B. Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs.
引用
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页码:51 / 59
页数:9
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