转录因子PLZF指导NKT细胞谱系的效应程序。
The transcription factor PLZF directs the effector program of the NKT cell lineage.
作者信息
Savage Adam K, Constantinides Michael G, Han Jin, Picard Damien, Martin Emmanuel, Li Bofeng, Lantz Olivier, Bendelac Albert
机构信息
Howard Hughes Medical Institute, Committee on Immunology, Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
出版信息
Immunity. 2008 Sep 19;29(3):391-403. doi: 10.1016/j.immuni.2008.07.011. Epub 2008 Aug 14.
The transcriptional control of CD1d-restricted NKT cell development has remained elusive. We report that PLZF (promyelocytic leukemia zinc finger, Zbtb16), a member of the BTB/POZ-ZF family of transcription factors that includes the CD4-lineage-specific c-Krox (Th-POK), is exquisitely specific to CD1d-restricted NKT cells and human MR1-specific MAIT cells. PLZF was induced immediately after positive selection of NKT cell precursors, and PLZF-deficient NKT cells failed to undergo the intrathymic expansion and effector differentiation that characterize their lineage. Instead, they preserved a naive phenotype and were directed to lymph nodes. Conversely, transgenic expression of PLZF induced CD4(+) thymocytes to acquire effector differentiation and migrate to nonlymphoid tissues. We suggest that PLZF is a transcriptional signature of NKT cells that directs their innate-like effector differentiation during thymic development.
CD1d限制性自然杀伤T细胞（NKT细胞）发育的转录调控机制一直难以捉摸。我们报告称，早幼粒细胞白血病锌指蛋白（PLZF，Zbtb16），作为转录因子BTB/POZ-ZF家族的一员，其中还包括CD4谱系特异性的c-Krox（Th-POK），对CD1d限制性NKT细胞和人类MR1特异性黏膜相关恒定T细胞（MAIT细胞）具有高度特异性。在NKT细胞前体阳性选择后，PLZF立即被诱导表达，而缺乏PLZF的NKT细胞无法经历胸腺内扩增以及作为其谱系特征的效应分化。相反，它们保留了幼稚表型并被导向淋巴结。相反，PLZF的转基因表达诱导CD4(+)胸腺细胞获得效应分化并迁移至非淋巴组织。我们认为，PLZF是NKT细胞的转录标志，在胸腺发育过程中指导其固有样效应分化。
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