Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion.
T cells develop in the thymus and are critical for adaptive immunity. Natural killer (NK) lymphocytes constitute an essential component of the innate immune system in tumor surveillance, reproduction, and defense against microbes and viruses. Here, we show that the transcription factor Bcl11b was expressed in all T cell compartments and was indispensable for T lineage development. When Bcl11b was deleted, T cells from all developmental stages acquired NK cell properties and concomitantly lost or decreased T cell-associated gene expression. These induced T-to-natural killer (ITNK) cells, which were morphologically and genetically similar to conventional NK cells, killed tumor cells in vitro, and effectively prevented tumor metastasis in vivo. Therefore, ITNKs may represent a new cell source for cell-based therapies.
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK.
Peng
P
Li
Shannon
S
Burke
Juexuan
J
Wang
Xiongfeng
X
Chen
Mariaestela
M
Ortiz
Song-Choon
SC
Lee
Dong
D
Lu
Lia
L
Campos
David
D
Goulding
Bee Ling
BL
Ng
Gordon
G
Dougan
Brian
B
Huntly
Bertie
B
Gottgens
Nancy A
NA
Jenkins
Neal G
NG
Copeland
Francesco
F
Colucci
Pentao
P
Liu
D000818:Animals; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D017353:Gene Deletion; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055879:Gene Knock-In Techniques; D019674:Genes, T-Cell Receptor beta; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D038041:Lymphopoiesis / Q000235:genetics; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology* / Q000637:transplantation; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
C511143:Bcl11b protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D013629:Tamoxifen; C016601:afimoxifene