Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs

Fernando Cruz-Guilloty, Matthew E. Pipkin, Ivana M. Djuretic, Ditsa Levanon, Joseph Lotem, Mathias G Lichtenheld, Yoram Groner, Anjana Rao

Research output: Contribution to journalArticle

238 Citations (Scopus)

Abstract

Activation of naive CD8 + T cells with antigen induces their differentiation into effector cytolytic T lymphocytes (CTLs). CTLs lyse infected or aberrant target cells by exocytosis of lytic granules containing the pore-forming protein perforin and a family of proteases termed granzymes. We show that effector CTL differentiation occurs in two sequential phases in vitro, characterized by early induction of T-bet and late induction of Eomesoder- min (Eomes), T-box transcription factors that regulate the early and late phases of inter- feron (IFN) γ expression, respectively. In addition, we demonstrate a critical role for the transcription factor Runx3 in CTL differentiation. Runx3 regulates Eomes expression as well as expression of three cardinal markers of the effector CTL program: IFN-γ, perforin, and granzyme B. Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs.

Original languageEnglish
Pages (from-to)51-59
Number of pages9
JournalJournal of Experimental Medicine
Volume206
Issue number1
DOIs
StatePublished - Jan 16 2009

Fingerprint

T-Lymphocytes
Proteins
Transcription Factors
Interferons
Granzymes
Porins
Perforin
Gene Regulatory Networks
Exocytosis
Peptide Hydrolases
Antigens
Genes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs. / Cruz-Guilloty, Fernando; Pipkin, Matthew E.; Djuretic, Ivana M.; Levanon, Ditsa; Lotem, Joseph; Lichtenheld, Mathias G; Groner, Yoram; Rao, Anjana.

In: Journal of Experimental Medicine, Vol. 206, No. 1, 16.01.2009, p. 51-59.

Research output: Contribution to journalArticle

Cruz-Guilloty, F, Pipkin, ME, Djuretic, IM, Levanon, D, Lotem, J, Lichtenheld, MG, Groner, Y & Rao, A 2009, 'Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs', Journal of Experimental Medicine, vol. 206, no. 1, pp. 51-59. https://doi.org/10.1084/jem.20081242
Cruz-Guilloty, Fernando ; Pipkin, Matthew E. ; Djuretic, Ivana M. ; Levanon, Ditsa ; Lotem, Joseph ; Lichtenheld, Mathias G ; Groner, Yoram ; Rao, Anjana. / Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs. In: Journal of Experimental Medicine. 2009 ; Vol. 206, No. 1. pp. 51-59.
@article{59b443881b22414b8a88903d255df760,
title = "Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs",
abstract = "Activation of naive CD8 + T cells with antigen induces their differentiation into effector cytolytic T lymphocytes (CTLs). CTLs lyse infected or aberrant target cells by exocytosis of lytic granules containing the pore-forming protein perforin and a family of proteases termed granzymes. We show that effector CTL differentiation occurs in two sequential phases in vitro, characterized by early induction of T-bet and late induction of Eomesoder- min (Eomes), T-box transcription factors that regulate the early and late phases of inter- feron (IFN) γ expression, respectively. In addition, we demonstrate a critical role for the transcription factor Runx3 in CTL differentiation. Runx3 regulates Eomes expression as well as expression of three cardinal markers of the effector CTL program: IFN-γ, perforin, and granzyme B. Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs.",
author = "Fernando Cruz-Guilloty and Pipkin, {Matthew E.} and Djuretic, {Ivana M.} and Ditsa Levanon and Joseph Lotem and Lichtenheld, {Mathias G} and Yoram Groner and Anjana Rao",
year = "2009",
month = "1",
day = "16",
doi = "10.1084/jem.20081242",
language = "English",
volume = "206",
pages = "51--59",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "1",

}

TY - JOUR

T1 - Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs

AU - Cruz-Guilloty, Fernando

AU - Pipkin, Matthew E.

AU - Djuretic, Ivana M.

AU - Levanon, Ditsa

AU - Lotem, Joseph

AU - Lichtenheld, Mathias G

AU - Groner, Yoram

AU - Rao, Anjana

PY - 2009/1/16

Y1 - 2009/1/16

N2 - Activation of naive CD8 + T cells with antigen induces their differentiation into effector cytolytic T lymphocytes (CTLs). CTLs lyse infected or aberrant target cells by exocytosis of lytic granules containing the pore-forming protein perforin and a family of proteases termed granzymes. We show that effector CTL differentiation occurs in two sequential phases in vitro, characterized by early induction of T-bet and late induction of Eomesoder- min (Eomes), T-box transcription factors that regulate the early and late phases of inter- feron (IFN) γ expression, respectively. In addition, we demonstrate a critical role for the transcription factor Runx3 in CTL differentiation. Runx3 regulates Eomes expression as well as expression of three cardinal markers of the effector CTL program: IFN-γ, perforin, and granzyme B. Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs.

AB - Activation of naive CD8 + T cells with antigen induces their differentiation into effector cytolytic T lymphocytes (CTLs). CTLs lyse infected or aberrant target cells by exocytosis of lytic granules containing the pore-forming protein perforin and a family of proteases termed granzymes. We show that effector CTL differentiation occurs in two sequential phases in vitro, characterized by early induction of T-bet and late induction of Eomesoder- min (Eomes), T-box transcription factors that regulate the early and late phases of inter- feron (IFN) γ expression, respectively. In addition, we demonstrate a critical role for the transcription factor Runx3 in CTL differentiation. Runx3 regulates Eomes expression as well as expression of three cardinal markers of the effector CTL program: IFN-γ, perforin, and granzyme B. Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs.

UR - http://www.scopus.com/inward/record.url?scp=60549090859&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=60549090859&partnerID=8YFLogxK

U2 - 10.1084/jem.20081242

DO - 10.1084/jem.20081242

M3 - Article

VL - 206

SP - 51

EP - 59

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 1

ER -