Mullen A C, High F A, Hutchins A S, Lee H W, Villarino A V, Livingston D M, Kung A L, Cereb N, Yao T P, Yang S Y, Reiner S L
Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.
Science. 2001 Jun 8;292(5523):1907-10. doi: 10.1126/science.1059835.
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.
细胞因子如何控制辅助性T（TH）细胞的分化仍存在争议。我们发现，T-bet在没有白细胞介素12（IL-12）/信号转导和转录激活因子4（STAT4）明显协助的情况下，通过将染色质重塑靶向单个干扰素-γ（IFN-γ）等位基因并诱导IL-12受体β2表达，来决定TH1效应细胞的命运。随后，IL-12/STAT4似乎在TH1细胞的发育中发挥了两个重要功能：作为生长信号，诱导存活和细胞分裂；作为反式激活因子，通过与共激活因子CREB结合蛋白的基因相互作用延长IFN-γ的合成。这些结果表明，细胞因子不仅仅诱导TH细胞命运的选择，相反，它可能作为一种重要的次级刺激，介导一个谱系的选择性存活。
