期刊
IMMUNITY
卷 42, 期 5, 页码 877-889出版社
CELL PRESS
DOI: 10.1016/j.immuni.2015.04.014
关键词
-
类别
资金
- Intramural Research Programs of NIAMS
- Ministry of Education, Culture, Sports, Science and Technology (Japan) [25893032]
- Astellas Foundation for Research on Metabolic Disorders
- Uehara Memorial Foundation
- Osaka Foundation for Promotion of Fundamental Medical Research
- Kanae Foundation for the Promotion of Medical Science
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [25893032, 15K08522] Funding Source: KAKEN
Interleukin-6 (IL-6) and IL-27 signal through a shared receptor subunit and employ the same downstream STAT transcription proteins, but yet are ascribed unique and overlapping functions. To evaluate the specificity and redundancy for these cytokines, we quantified their global transcriptomic changes and determined the relative contributions of STAT1 and STAT3 using genetic models and chromatin immunoprecipitation- sequencing (ChIP-seq) approaches. We found an extensive overlap of the transcriptomes induced by IL-6 and IL-27 and few examples in which the cytokines acted in opposition. Using STAT-deficient cells and T cells from patients with gain-of-function STAT1 mutations, we demonstrated that STAT3 is responsible for the overall transcriptional output driven by both cytokines, whereas STAT1 is the principal driver of specificity. STAT1 cannot compensate in the absence of STAT3 and, in fact, much of STAT1 binding to chromatin is STAT3 dependent. Thus, STAT1 shapes the specific cytokine signature superimposed upon STAT3's action.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据