Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs

被引:366
作者
Cruz-Guilloty, Fernando [1 ,2 ]
Pipkin, Matthew E. [1 ,2 ]
Djuretic, Ivana M. [1 ,2 ]
Levanon, Ditsa [3 ]
Lotem, Joseph [3 ]
Lichtenheld, Mathias G. [4 ]
Groner, Yoram [3 ]
Rao, Anjana [1 ,2 ]
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
收藏
页码:51 / 59
页数:9
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