美国芝加哥大学Nicolas Chevrier团队近期取得重要工作进展，他们通过利用成对细胞因子编码来解释机体对败血症的反应。相关研究成果2024年1月8日在线发表于《自然—免疫学》杂志上。

据介绍，败血症是对感染的一种系统反应，具有危及生命的后果。人们对败血症跨器官的分子和细胞影响目前还处于初级阶段。

研究人员通过测量器官间基因表达的动态变化来表征败血症的发病机制。为了确定败血症中控制器官状态的分子，研究人员将败血症对器官基因表达的影响与6种单一和15种成对重组细胞因子的影响进行了比较。研究人员发现，肿瘤坏死因子加白细胞介素（IL）-18、干扰素γ或IL-1β的成对作用足以反映败血症对组织的影响。

从机制上讲，研究人员通过计算9个器官中195种细胞类型的丰度变化，绘制了败血症和细胞因子的细胞效应图，并通过全小鼠空间分析进行了验证。

总之，这一工作将败血症中的细胞因子杂音解码为成对的细胞因子信息，捕捉宿主对疾病的基因、细胞和组织反应。

附：英文原文

Title: A pairwise cytokine code explains the organism-wide response to sepsis

Author: Takahama, Michihiro, Patil, Ashwini, Richey, Gabriella, Cipurko, Denis, Johnson, Katherine, Carbonetto, Peter, Plaster, Madison, Pandey, Surya, Cheronis, Katerina, Ueda, Tatsuki, Gruenbaum, Adam, Kawamoto, Tadafumi, Stephens, Matthew, Chevrier, Nicolas

Issue&Volume: 2024-01-08

Abstract: Sepsis is a systemic response to infection with life-threatening consequences. Our understanding of the molecular and cellular impact of sepsis across organs remains rudimentary. Here, we characterize the pathogenesis of sepsis by measuring dynamic changes in gene expression across organs. To pinpoint molecules controlling organ states in sepsis, we compare the effects of sepsis on organ gene expression to those of 6 singles and 15 pairs of recombinant cytokines. Strikingly, we find that the pairwise effects of tumor necrosis factor plus interleukin (IL)-18, interferon-gamma or IL-1β suffice to mirror the impact of sepsis across tissues. Mechanistically, we map the cellular effects of sepsis and cytokines by computing changes in the abundance of 195 cell types across 9 organs, which we validate by whole-mouse spatial profiling. Our work decodes the cytokine cacophony in sepsis into a pairwise cytokine message capturing the gene, cell and tissue responses of the host to the disease.

DOI: 10.1038/s41590-023-01722-8

Source: https://www.nature.com/articles/s41590-023-01722-8