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

作者：Fernando Cruz‐Guilloty, Matthew E. Pipkin, Ivana M. Djuretic, Ditsa Levanon, Joseph Lotem, Mathias Georg Lichtenheld, Yoram Groner, Anjana Rao · 发表于：The Journal of Experimental Medicine · 年份：2009 · DOI：10.1084/jem.20081242 · 被引用次数：531 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、Immunotherapy and Immune Responses

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.