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研究解析自然杀伤细胞中的全局性细胞因子信号网络
作者:小柯机器人 发布时间:2021/4/18 17:56:56

美国斯隆凯特琳癌症研究中心Colleen M. Lau、Joseph C. Sun等研究人员合作解析自然杀伤细胞中的全局性细胞因子信号网络。相关论文于2021年4月15日在线发表在《自然—免疫学》杂志上。

研究人员采用了一种多组学方法来解构和重建自然杀伤(NK)细胞中多个细胞因子信号通路的复杂相互作用。促炎细胞因子和稳态细胞因子形成一个共同的信号轴,共同调节整体基因表达并进一步抑制由I型干扰素信号传导诱导的表达。这些细胞因子通过STAT蛋白介导表观遗传调控的不同模式,并且集体信号传导最能概括全局性抗病毒反应。响应最活跃的基因在人类和小鼠之间都很保守,其中包括细胞因子STAT诱导的交叉调控程序。因此,在控制NK细胞应答的细胞因子信号传导途径之间存在复杂的串扰。

据悉,通过STAT蛋白的细胞因子信号传导对于NK细胞的最佳抗病毒反应至关重要。但是,细胞因子和STAT信号均具有多效性,因此无法将分子变化精确地归因于特定的细胞因子STAT模块。

附:英文原文

Title: Deconvoluting global cytokine signaling networks in natural killer cells

Author: Gabriela M. Wiedemann, Endi K. Santosa, Simon Grassmann, Sam Sheppard, Jean-Benot Le Luduec, Nicholas M. Adams, Celeste Dang, Katharine C. Hsu, Joseph C. Sun, Colleen M. Lau

Issue&Volume: 2021-04-15

Abstract: Cytokine signaling via signal transducer and activator of transcription (STAT) proteins is crucial for optimal antiviral responses of natural killer (NK) cells. However, the pleiotropic effects of both cytokine and STAT signaling preclude the ability to precisely attribute molecular changes to specific cytokine–STAT modules. Here, we employed a multi-omics approach to deconstruct and rebuild the complex interaction of multiple cytokine signaling pathways in NK cells. Proinflammatory cytokines and homeostatic cytokines formed a cooperative axis to commonly regulate global gene expression and to further repress expression induced by type I interferon signaling. These cytokines mediated distinct modes of epigenetic regulation via STAT proteins, and collective signaling best recapitulated global antiviral responses. The most dynamically responsive genes were conserved across humans and mice, which included a cytokine–STAT-induced cross-regulatory program. Thus, an intricate crosstalk exists between cytokine signaling pathways, which governs NK cell responses.

DOI: 10.1038/s41590-021-00909-1

Source: https://www.nature.com/articles/s41590-021-00909-1

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex