Asymmetric Action of STAT Transcription Factors Drives Transcriptional Outputs and Cytokine Specificity

被引：114

作者：

Hirahara, Kiyoshi ^{[1
,7
]}

Onodera, Atsushi ^{[8
]}

Villarino, Alejandro V. ^{[1
]}

Bonelli, Michael ^{[1
]}

Sciume, Giuseppe ^{[1
]}

Laurence, Arian ^{[1
]}

Sun, Hong-Wei ^{[2
]}

Brooks, Stephen R. ^{[2
]}

Vahedi, Golnaz ^{[1
]}

Shih, Han-Yu ^{[1
]}

Gutierrez-Cruz, Gustavo ^{[3
]}

Iwata, Shigeru ^{[1
]}

Suzuki, Ryo ^{[4
]}

Mikami, Yohei ^{[1
]}

Okamoto, Yoshitaka ^{[9
]}

Nakayama, Toshinori ^{[8
,10
]}

Holland, Steven M. ^{[5
]}

Hunter, Christopher A. ^{[6
]}

Kanno, Yuka ^{[1
]}

O'Shea, John J. ^{[1
]}

机构：

[1] NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA

[2] NIAMS, Biodata Min & Discovery Sect, NIH, Bethesda, MD 20892 USA

[3] NIAMS, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA

[4] NIAMS, Lab Mol Immunogenet, NIH, Bethesda, MD 20892 USA

[5] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA

[6] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA

[7] Chiba Univ, Grad Sch Med, Dept Adv Allergol Airway, Chiba 2608670, Japan

[8] Chiba Univ, Grad Sch Med, Dept Immunol, Chiba 2608670, Japan

[9] Chiba Univ, Grad Sch Med, Dept Otorhinolaryngol, Chiba 2608670, Japan

[10] Core Res Evolut Sci & Technol, Japan Sci & Technol Agcy, Chiba, Chiba 2608670, Japan

来源：

IMMUNITY | 2015年 / 42卷 / 05期

关键词：

CD4(+) T-CELLS; INTERFERON-GAMMA; CUTTING EDGE; TH17; CELLS; IL-27; INTERLEUKIN-27; ACTIVATION; RECEPTOR; DIFFERENTIATION; INDUCTION;

D O I：

10.1016/j.immuni.2015.04.014

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：877 / 889

页数：13

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