The transcription factor PLZF directs the effector program of the NKT cell lineage

被引:576
作者
Savage, Adam K. [1 ]
Constantinides, Michael G. [1 ]
Han, Jin [1 ]
Picard, Damien [1 ]
Martin, Emmanuel [2 ,3 ]
Li, Bofeng [4 ]
Lantz, Olivier [2 ,3 ]
Bendelac, Albert [1 ]
机构
[1] Univ Chicago, Dept Pathol, Comm Immunol, Howard Hughes Med Inst, Chicago, IL 60637 USA
[2] Inst Curie, INSERM, Immunol Lab, F-75005 Paris, France
[3] Inst Curie, INSERM, Unite 653, F-75005 Paris, France
[4] Univ Chicago, Comm Immunol, Dept Med Pathol & Pediat, Chicago, IL 60637 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/j.immuni.2008.07.011
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:391 / 403
页数:13
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