Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch

Derk Amsen; Andrey Antov; Dragana Jankovic; Alan Sher; Freddy Radtke; Abdallah Souabni; Meinrad Busslinger; Brent McCright; Thomas Gridley; Richard A. Flavell

doi:https://doi.org/10.1016/j.immuni.2007.05.021

Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch

Derk Amsen, Andrey Antov, Dragana Jankovic, Alan Sher, Freddy Radtke, Abdallah Souabni, Meinrad Busslinger, Brent McCright, Thomas Gridley, Richard A. Flavell

Research output: Contribution to journal › Article › Academic › peer-review

339 Citations (Scopus)

Abstract

CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using T cell-specific gene ablation of the Notch effector RBP-J or the Notch1 and 2 receptors, we showed here that Notch was required on CD4(+) T cells for physiological Th2 responses to parasite antigens. GATA-3 was necessary for Notch-induced Th2 differentiation, and we identified an upstream Gata3 promoter as a direct target for Notch signaling. Moreover, absence of GATA-3 turned Notch from a Th2 inducer into a powerful inducer of Th1 differentiation. Therefore, Gata3 is a critical element determining inductive Th2 differentiation and limiting Th1 differentiation by Notch

Original language	English
Pages (from-to)	89-99
Journal	Immunity
Volume	27
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2007.05.021
Publication status	Published - 2007

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https://doi.org/10.1016/j.immuni.2007.05.021

Cite this

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title = "Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch",

abstract = "CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using T cell-specific gene ablation of the Notch effector RBP-J or the Notch1 and 2 receptors, we showed here that Notch was required on CD4(+) T cells for physiological Th2 responses to parasite antigens. GATA-3 was necessary for Notch-induced Th2 differentiation, and we identified an upstream Gata3 promoter as a direct target for Notch signaling. Moreover, absence of GATA-3 turned Notch from a Th2 inducer into a powerful inducer of Th1 differentiation. Therefore, Gata3 is a critical element determining inductive Th2 differentiation and limiting Th1 differentiation by Notch",

author = "Derk Amsen and Andrey Antov and Dragana Jankovic and Alan Sher and Freddy Radtke and Abdallah Souabni and Meinrad Busslinger and Brent McCright and Thomas Gridley and Flavell, {Richard A.}",

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doi = "https://doi.org/10.1016/j.immuni.2007.05.021",

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T1 - Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch

AU - Amsen, Derk

AU - Antov, Andrey

AU - Jankovic, Dragana

AU - Sher, Alan

AU - Radtke, Freddy

AU - Souabni, Abdallah

AU - Busslinger, Meinrad

AU - McCright, Brent

AU - Gridley, Thomas

AU - Flavell, Richard A.

PY - 2007

Y1 - 2007

N2 - CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using T cell-specific gene ablation of the Notch effector RBP-J or the Notch1 and 2 receptors, we showed here that Notch was required on CD4(+) T cells for physiological Th2 responses to parasite antigens. GATA-3 was necessary for Notch-induced Th2 differentiation, and we identified an upstream Gata3 promoter as a direct target for Notch signaling. Moreover, absence of GATA-3 turned Notch from a Th2 inducer into a powerful inducer of Th1 differentiation. Therefore, Gata3 is a critical element determining inductive Th2 differentiation and limiting Th1 differentiation by Notch

AB - CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using T cell-specific gene ablation of the Notch effector RBP-J or the Notch1 and 2 receptors, we showed here that Notch was required on CD4(+) T cells for physiological Th2 responses to parasite antigens. GATA-3 was necessary for Notch-induced Th2 differentiation, and we identified an upstream Gata3 promoter as a direct target for Notch signaling. Moreover, absence of GATA-3 turned Notch from a Th2 inducer into a powerful inducer of Th1 differentiation. Therefore, Gata3 is a critical element determining inductive Th2 differentiation and limiting Th1 differentiation by Notch

U2 - https://doi.org/10.1016/j.immuni.2007.05.021

DO - https://doi.org/10.1016/j.immuni.2007.05.021

M3 - Article

C2 - 17658279

SN - 1074-7613

VL - 27

SP - 89

EP - 99

JO - Immunity

JF - Immunity

IS - 1

ER -