title: Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells.
abstract: The transcriptional repressor Blimp-1 promotes the differentiation of CD8(+) T cells into short-lived effector cells (SLECs) that express the lectin-like receptor KLRG-1, but how it operates remains poorly defined. Here we show that Blimp-1 bound to and repressed the promoter of the gene encoding the DNA-binding inhibitor Id3 in SLECs. Repression of Id3 by Blimp-1 was dispensable for SLEC development but limited the ability of SLECs to persist as memory cells. Enforced expression of Id3 was sufficient to restore SLEC survival and enhanced recall responses. Id3 function was mediated in part through inhibition of the transcriptional activity of E2A and induction of genes regulating genome stability. Our findings identify the Blimp-1-Id3-E2A axis as a key molecular switch that determines whether effector CD8(+) T cells are programmed to die or enter the memory pool.
authors: Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
authors: Yun
authors: Y
authors: Ji
authors: Zoltan
authors: Z
authors: Pos
authors: Mahadev
authors: M
authors: Rao
authors: Christopher A
authors: CA
authors: Klebanoff
authors: Zhiya
authors: Z
authors: Yu
authors: Madhusudhanan
authors: M
authors: Sukumar
authors: Robert N
authors: RN
authors: Reger
authors: Douglas C
authors: DC
authors: Palmer
authors: Zachary A
authors: ZA
authors: Borman
authors: Pawel
authors: P
authors: Muranski
authors: Ena
authors: E
authors: Wang
authors: David S
authors: DS
authors: Schrump
authors: Francesco M
authors: FM
authors: Marincola
authors: Nicholas P
authors: NP
authors: Restifo
authors: Luca
authors: L
authors: Gattinoni
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D004260:DNA Repair; D004261:DNA Replication; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007156:Immunologic Memory / Q000276:immunology*; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011401:Promoter Regions, Genetic; D011971:Receptors, Immunologic / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D037181:Lectins, C-Type; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011971:Receptors, Immunologic; D014157:Transcription Factors; C497452:Idb2 protein, mouse; C451496:Klrg1 protein, mouse; C513258:Prdm1 protein, mouse; C075668:Tcf3 protein, mouse; C067679:Idb3 protein, mouse