The transcription factor PLZF directs the effector program of the NKT cell lineage.
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.
Savage
Adam K
AK
Howard Hughes Medical Institute, Committee on Immunology, Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Constantinides
Michael G
MG
Han
Jin
J
Picard
Damien
D
Martin
Emmanuel
E
Li
Bofeng
B
Lantz
Olivier
O
Bendelac
Albert
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C513267:Zbtb16 protein, mouse; C092037:ZBTB16 protein, human