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

被引：670

作者：

Mullen, AC

High, FA

Hutchins, AS

Lee, HW

Villarino, AV

Livingston, DM

Kung, AL

Cereb, N

Yao, TP

Yang, SY

Reiner, SL ^{[1
]}

机构：

[1] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

[2] Univ Penn, Dept Med, Philadelphia, PA 19104 USA

[3] Dana Farber Canc Inst, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston, MA 02115 USA

[5] Histogenet Inc, Hawthorne, NY 10532 USA

[6] Ctr Genet Polymorphism, Hawthorne, NY 10532 USA

[7] Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA

来源：

SCIENCE | 2001年 / 292卷 / 5523期

关键词：

D O I：

10.1126/science.1059835

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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(H)1 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 T(H)1 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 T-H fate choice but instead may act as an essential secondary stimulus that mediates selective survival of a lineage.

引用

页码：1907 / 1910

页数：4

共 29 条

[1] Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation [J].