美国加州大学洛杉矶分校Alexander Hoffmann团队发现，六种不同的NFκB信号编码各自的信号来区分刺激，并实现正确的巨噬细胞应答。该项研究成果发表在2021年5月11日出版的《免疫》杂志上。

研究人员检查了有关刺激的信息如何在NFκB活性的动力学中进行编码。研究人员生成了mVenus-RelA报告基因小鼠系，能够对响应宿主和病原体产生刺激的原代巨噬细胞进行高通量活细胞分析。信息理论的工作流程确定了六个动态特征（称为信号密码子），这些特征将刺激信息传递到细胞核。

具体而言，振荡轨迹是对细胞因子反应的标志，而不是病原体衍生的刺激标志。舍格伦综合征小鼠模型中巨噬细胞的单细胞成像和RNA测序揭示了对刺激的不适当反应，这暗示了两个NFκB信号密码子的混淆。因此，NFκB信号的动态通过六个信号密码子对免疫威胁进行分类，并且基于缺陷密码子部署的信号混淆可能是某些炎症性疾病的病因。

据悉，巨噬细胞通过转录因子NFκB引发炎症反应。NFκB活性的时间模式决定了哪些基因被表达，从而决定了随之而来的反应类型。

附：英文原文

Title: Six distinct NFκB signaling codons convey discrete information to distinguish stimuli and enable appropriate macrophage responses

Author: Adewunmi Adelaja, Brooks Taylor, Katherine M. Sheu, Yi Liu, Stefanie Luecke, Alexander Hoffmann

Issue&Volume: 2021/05/11

Abstract: Macrophages initiate inflammatory responses via the transcription factor NFκB. The temporal pattern of NFκB activity determines which genes are expressed and thus, the type of response that ensues. Here, we examined how information about the stimulus is encoded in the dynamics of NFκB activity. We generated an mVenus-RelA reporter mouse line to enable high-throughput live-cell analysis of primary macrophages responding to host- and pathogen-derived stimuli. An information-theoretic workflow identified six dynamical features—termed signaling codons—that convey stimulus information to the nucleus. In particular, oscillatory trajectories were a hallmark of responses to cytokine but not pathogen-derived stimuli. Single-cell imaging and RNA sequencing of macrophages from a mouse model of Sjgren’s syndrome revealed inappropriate responses to stimuli, suggestive of confusion of two NFκB signaling codons. Thus, the dynamics of NFκB signaling classify immune threats through six signaling codons, and signal confusion based on defective codon deployment may underlie the etiology of some inflammatory diseases.

DOI: 10.1016/j.immuni.2021.04.011

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00173-4