Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells

Derk Amsen; J. Magarian Blander; Gap Ryol Lee; Kenji Tanigaki; Tasuku Honjo; Richard A. Flavell

doi:https://doi.org/10.1016/S0092-8674(04)00451-9

Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells

Derk Amsen, J. Magarian Blander, Gap Ryol Lee, Kenji Tanigaki, Tasuku Honjo, Richard A. Flavell

Landsteiner Laboratory (AMC)

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

775 Citations (Scopus)

Abstract

Antigen-presenting cells (APC) tailor immune responses to microbial encounters by stimulating differentiation of CD4 T cells into the Th1 and Th2 lineages. We demonstrate that APC use the Notch pathway to instruct T cell differentiation. Strikingly, of the two Notch ligand families, Delta induces Th1, while Jagged induces the alternate Th2 fate. Expression of these different Notch ligands on APC is induced by Th1- or Th2-promoting stimuli. Th2 differentiation has been considered a default process as APC-derived instructive signals are unknown. We demonstrate that Jagged constitutes an instructive signal for Th2 differentiation, which is independent of IL4/STAT6. Th2 differentiation induced by APC is abrogated in T cells lacking the Notch effector RBPJkappa. Notch directs Th2 differentiation by inducing GATA3 and by directly regulating il4 gene transcription through RBPJkappa sites in a 3' enhancer

Original language	English
Pages (from-to)	515-526
Journal	Cell
Volume	117
Issue number	4
DOIs	https://doi.org/10.1016/S0092-8674(04)00451-9
Publication status	Published - 2004

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https://doi.org/10.1016/S0092-8674(04)00451-9

Cite this

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title = "Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells",

abstract = "Antigen-presenting cells (APC) tailor immune responses to microbial encounters by stimulating differentiation of CD4 T cells into the Th1 and Th2 lineages. We demonstrate that APC use the Notch pathway to instruct T cell differentiation. Strikingly, of the two Notch ligand families, Delta induces Th1, while Jagged induces the alternate Th2 fate. Expression of these different Notch ligands on APC is induced by Th1- or Th2-promoting stimuli. Th2 differentiation has been considered a default process as APC-derived instructive signals are unknown. We demonstrate that Jagged constitutes an instructive signal for Th2 differentiation, which is independent of IL4/STAT6. Th2 differentiation induced by APC is abrogated in T cells lacking the Notch effector RBPJkappa. Notch directs Th2 differentiation by inducing GATA3 and by directly regulating il4 gene transcription through RBPJkappa sites in a 3' enhancer",

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T1 - Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells

AU - Amsen, Derk

AU - Blander, J. Magarian

AU - Lee, Gap Ryol

AU - Tanigaki, Kenji

AU - Honjo, Tasuku

AU - Flavell, Richard A.

PY - 2004

Y1 - 2004

N2 - Antigen-presenting cells (APC) tailor immune responses to microbial encounters by stimulating differentiation of CD4 T cells into the Th1 and Th2 lineages. We demonstrate that APC use the Notch pathway to instruct T cell differentiation. Strikingly, of the two Notch ligand families, Delta induces Th1, while Jagged induces the alternate Th2 fate. Expression of these different Notch ligands on APC is induced by Th1- or Th2-promoting stimuli. Th2 differentiation has been considered a default process as APC-derived instructive signals are unknown. We demonstrate that Jagged constitutes an instructive signal for Th2 differentiation, which is independent of IL4/STAT6. Th2 differentiation induced by APC is abrogated in T cells lacking the Notch effector RBPJkappa. Notch directs Th2 differentiation by inducing GATA3 and by directly regulating il4 gene transcription through RBPJkappa sites in a 3' enhancer

AB - Antigen-presenting cells (APC) tailor immune responses to microbial encounters by stimulating differentiation of CD4 T cells into the Th1 and Th2 lineages. We demonstrate that APC use the Notch pathway to instruct T cell differentiation. Strikingly, of the two Notch ligand families, Delta induces Th1, while Jagged induces the alternate Th2 fate. Expression of these different Notch ligands on APC is induced by Th1- or Th2-promoting stimuli. Th2 differentiation has been considered a default process as APC-derived instructive signals are unknown. We demonstrate that Jagged constitutes an instructive signal for Th2 differentiation, which is independent of IL4/STAT6. Th2 differentiation induced by APC is abrogated in T cells lacking the Notch effector RBPJkappa. Notch directs Th2 differentiation by inducing GATA3 and by directly regulating il4 gene transcription through RBPJkappa sites in a 3' enhancer

U2 - https://doi.org/10.1016/S0092-8674(04)00451-9

DO - https://doi.org/10.1016/S0092-8674(04)00451-9

M3 - Article

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SN - 0092-8674

VL - 117

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