| Autor: |
Ji Y; Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA., Pos Z, Rao M, Klebanoff CA, Yu Z, Sukumar M, Reger RN, Palmer DC, Borman ZA, Muranski P, Wang E, Schrump DS, Marincola FM, Restifo NP, Gattinoni L |
| Jazyk: |
angličtina |
| Zdroj: |
Nature immunology [Nat Immunol] 2011 Nov 06; Vol. 12 (12), pp. 1230-7. Date of Electronic Publication: 2011 Nov 06. |
| DOI: |
10.1038/ni.2153 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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