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

Publication ,  Journal Article
Mullen, AC; High, FA; Hutchins, AS; Lee, HW; Villarino, AV; Livingston, DM; Kung, AL; Cereb, N; Yao, TP; Yang, SY; Reiner, SL
Published in: Science
June 8, 2001

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-gamma (IFN-gamma) alleles and by inducing IL-12 receptor beta2 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-gamma 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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Published In

Science

DOI

ISSN

0036-8075

Publication Date

June 8, 2001

Volume

292

Issue

5523

Start / End Page

1907 / 1910

Location

United States

Related Subject Headings

  • Transcription Factors
  • Trans-Activators
  • Th1 Cells
  • T-Box Domain Proteins
  • Signal Transduction
  • STAT4 Transcription Factor
  • Receptors, Interleukin-12
  • Receptors, Interleukin
  • RNA, Messenger
  • Nuclear Proteins
 

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Mullen, A. C., High, F. A., Hutchins, A. S., Lee, H. W., Villarino, A. V., Livingston, D. M., … Reiner, S. L. (2001). Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science, 292(5523), 1907–1910. https://doi.org/10.1126/science.1059835
Mullen, A. C., F. A. High, A. S. Hutchins, H. W. Lee, A. V. Villarino, D. M. Livingston, A. L. Kung, et al. “Role of T-bet in commitment of TH1 cells before IL-12-dependent selection.Science 292, no. 5523 (June 8, 2001): 1907–10. https://doi.org/10.1126/science.1059835.
Mullen AC, High FA, Hutchins AS, Lee HW, Villarino AV, Livingston DM, et al. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science. 2001 Jun 8;292(5523):1907–10.
Mullen, A. C., et al. “Role of T-bet in commitment of TH1 cells before IL-12-dependent selection.Science, vol. 292, no. 5523, June 2001, pp. 1907–10. Pubmed, doi:10.1126/science.1059835.
Mullen AC, High FA, Hutchins AS, Lee HW, Villarino AV, Livingston DM, Kung AL, Cereb N, Yao TP, Yang SY, Reiner SL. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science. 2001 Jun 8;292(5523):1907–1910.
Journal cover image

Published In

Science

DOI

ISSN

0036-8075

Publication Date

June 8, 2001

Volume

292

Issue

5523

Start / End Page

1907 / 1910

Location

United States

Related Subject Headings

  • Transcription Factors
  • Trans-Activators
  • Th1 Cells
  • T-Box Domain Proteins
  • Signal Transduction
  • STAT4 Transcription Factor
  • Receptors, Interleukin-12
  • Receptors, Interleukin
  • RNA, Messenger
  • Nuclear Proteins