Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8 + T cells

Yun Ji, Z. Pós, Mahadev Rao, Christopher A. Klebanoff, Zhiya Yu, Madhusudhanan Sukumar, Robert N. Reger, Douglas C. Palmer, Zachary A. Borman, Pawel Muranski, Ena Wang, David S. Schrump, Francesco M. Marincola, Nicholas P. Restifo, Luca Gattinoni

Research output: Article

95 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1230-1237
Number of pages8
JournalNature Immunology
Volume12
Issue number12
DOIs
Publication statusPublished - dec. 2011

Fingerprint

T-Lymphocytes
DNA
Mitogen Receptors
Aptitude
Genomic Instability
Genes
Cell Survival

ASJC Scopus subject areas

  • Immunology

Cite this

Ji, Y., Pós, Z., Rao, M., Klebanoff, C. A., Yu, Z., Sukumar, M., ... Gattinoni, L. (2011). Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8 + T cells. Nature Immunology, 12(12), 1230-1237. https://doi.org/10.1038/ni.2153

Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8 + T cells. / Ji, Yun; Pós, Z.; Rao, Mahadev; Klebanoff, Christopher A.; Yu, Zhiya; Sukumar, Madhusudhanan; Reger, Robert N.; Palmer, Douglas C.; Borman, Zachary A.; Muranski, Pawel; Wang, Ena; Schrump, David S.; Marincola, Francesco M.; Restifo, Nicholas P.; Gattinoni, Luca.

In: Nature Immunology, Vol. 12, No. 12, 12.2011, p. 1230-1237.

Research output: Article

Ji, Y, Pós, 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 2011, 'Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8 + T cells', Nature Immunology, vol. 12, no. 12, pp. 1230-1237. https://doi.org/10.1038/ni.2153
Ji, Yun ; Pós, Z. ; Rao, Mahadev ; Klebanoff, Christopher A. ; Yu, Zhiya ; Sukumar, Madhusudhanan ; Reger, Robert N. ; Palmer, Douglas C. ; Borman, Zachary A. ; Muranski, Pawel ; Wang, Ena ; Schrump, David S. ; Marincola, Francesco M. ; Restifo, Nicholas P. ; Gattinoni, Luca. / Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8 + T cells. In: Nature Immunology. 2011 ; Vol. 12, No. 12. pp. 1230-1237.
@article{38a705f8ffa0487aac657571f4ed5197,
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.",
author = "Yun Ji and Z. P{\'o}s and Mahadev Rao and Klebanoff, {Christopher A.} and Zhiya Yu and Madhusudhanan Sukumar and Reger, {Robert N.} and Palmer, {Douglas C.} and Borman, {Zachary A.} and Pawel Muranski and Ena Wang and Schrump, {David S.} and Marincola, {Francesco M.} and Restifo, {Nicholas P.} and Luca Gattinoni",
year = "2011",
month = "12",
doi = "10.1038/ni.2153",
language = "English",
volume = "12",
pages = "1230--1237",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8 + T cells

AU - Ji, Yun

AU - Pós, Z.

AU - Rao, Mahadev

AU - Klebanoff, Christopher A.

AU - Yu, Zhiya

AU - Sukumar, Madhusudhanan

AU - Reger, Robert N.

AU - Palmer, Douglas C.

AU - Borman, Zachary A.

AU - Muranski, Pawel

AU - Wang, Ena

AU - Schrump, David S.

AU - Marincola, Francesco M.

AU - Restifo, Nicholas P.

AU - Gattinoni, Luca

PY - 2011/12

Y1 - 2011/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=81255144750&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81255144750&partnerID=8YFLogxK

U2 - 10.1038/ni.2153

DO - 10.1038/ni.2153

M3 - Article

C2 - 22057288

AN - SCOPUS:81255144750

VL - 12

SP - 1230

EP - 1237

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 12

ER -