Role of T-bet in commitment of TH1 cells before IL- 12-dependent selection

A. C. Mullen; F. A. High; A. S. Hutchins; H. W. Lee; A. V. Villarino; D. M. Livingston; A. L. Kung; N. Cereb; T. P. Yao; S. Y. Yang; S. L. Reiner

doi:10.1126/science.1059835

Role of T-bet in commitment of T_H1 cells before IL- 12-dependent selection

A. C. Mullen, F. A. High, A. S. Hutchins, H. W. Lee, A. V. Villarino, D. M. Livingston, A. L. Kung, N. Cereb, T. P. Yao, S. Y. Yang, S. L. Reiner

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Abstract

How cytokines control differentiation of helper T (T_H) cells is controversial. We show that T-bet, without apparent assistance from interleukin 12 (IL-12)/STAT4, specifies T_H1 effector fate by targeting chromatin remodeling to individual interferon-γ (IFN-γ) alleles and by inducing IL-12 receptor β2 expression. Subsequently, it appears that IL- 12/STAT4 serves two essential functions in the development of T_H1 cells: as growth signal, inducing survival and cell division; and as trans-activator, prolonging IFN-γ synthesis through a genetic interaction with the coactivator, CREB-binding protein. These results suggest that a cytokine does not simply induce T_H fate choice but instead may act as an essential secondary stimulus that mediates selective survival of a lineage.

Original language	English (US)
Pages (from-to)	1907-1910
Number of pages	4
Journal	Science
Volume	292
Issue number	5523
DOIs	https://doi.org/10.1126/science.1059835
State	Published - Jun 8 2001
Externally published	Yes

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title = "Role of T-bet in commitment of TH1 cells before IL- 12-dependent selection",

abstract = "How cytokines control differentiation of helper T (TH) cells is controversial. We show that T-bet, without apparent assistance from interleukin 12 (IL-12)/STAT4, specifies TH1 effector fate by targeting chromatin remodeling to individual interferon-γ (IFN-γ) alleles and by inducing IL-12 receptor β2 expression. Subsequently, it appears that IL- 12/STAT4 serves two essential functions in the development of TH1 cells: as growth signal, inducing survival and cell division; and as trans-activator, prolonging IFN-γ synthesis through a genetic interaction with the coactivator, CREB-binding protein. These results suggest that a cytokine does not simply induce TH fate choice but instead may act as an essential secondary stimulus that mediates selective survival of a lineage.",

author = "Mullen, {A. C.} and High, {F. A.} and Hutchins, {A. S.} and Lee, {H. W.} and Villarino, {A. V.} and Livingston, {D. M.} and Kung, {A. L.} and N. Cereb and Yao, {T. P.} and Yang, {S. Y.} and Reiner, {S. L.}",

year = "2001",

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T1 - Role of T-bet in commitment of TH1 cells before IL- 12-dependent selection

AU - Mullen, A. C.

AU - High, F. A.

AU - Hutchins, A. S.

AU - Lee, H. W.

AU - Villarino, A. V.

AU - Livingston, D. M.

AU - Kung, A. L.

AU - Cereb, N.

AU - Yao, T. P.

AU - Yang, S. Y.

AU - Reiner, S. L.

PY - 2001/6/8

Y1 - 2001/6/8

N2 - How cytokines control differentiation of helper T (TH) cells is controversial. We show that T-bet, without apparent assistance from interleukin 12 (IL-12)/STAT4, specifies TH1 effector fate by targeting chromatin remodeling to individual interferon-γ (IFN-γ) alleles and by inducing IL-12 receptor β2 expression. Subsequently, it appears that IL- 12/STAT4 serves two essential functions in the development of TH1 cells: as growth signal, inducing survival and cell division; and as trans-activator, prolonging IFN-γ synthesis through a genetic interaction with the coactivator, CREB-binding protein. These results suggest that a cytokine does not simply induce TH fate choice but instead may act as an essential secondary stimulus that mediates selective survival of a lineage.

AB - How cytokines control differentiation of helper T (TH) cells is controversial. We show that T-bet, without apparent assistance from interleukin 12 (IL-12)/STAT4, specifies TH1 effector fate by targeting chromatin remodeling to individual interferon-γ (IFN-γ) alleles and by inducing IL-12 receptor β2 expression. Subsequently, it appears that IL- 12/STAT4 serves two essential functions in the development of TH1 cells: as growth signal, inducing survival and cell division; and as trans-activator, prolonging IFN-γ synthesis through a genetic interaction with the coactivator, CREB-binding protein. These results suggest that a cytokine does not simply induce TH fate choice but instead may act as an essential secondary stimulus that mediates selective survival of a lineage.

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Role of T-bet in commitment of T_H1 cells before IL- 12-dependent selection

Abstract

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