通过测量细胞信号转导通路活性来定量表征免疫细胞。
Quantitative characterization of immune cells by measuring cellular signal transduction pathway activity.
发表日期:2024 Oct 18
作者:
Wilbert Bouwman, Wim Verhaegh, Arie van Doorn, Reinier Raymakers, Tom van der Poll, Anja van de Stolpe
来源:
ARTHRITIS RESEARCH & THERAPY
摘要:
对于许多疾病,包括癌症、感染和自身免疫性疾病,免疫反应是疾病进展、治疗反应和临床结果的主要决定因素。先天性和适应性免疫反应由不同免疫细胞类型的协调活动控制。免疫细胞的功能活动状态由信号转导途径(STP)决定。最近开发的技术(基于同步转录组的信号转导通路活性分析,STAP-STP)能够基于 mRNA 分析同时定量测量免疫细胞中相关 STP 的活性。 STAP-STP技术用于分析多种免疫细胞类型在静息和激活功能状态下的公开转录组数据。此外,还分析了类风湿性关节炎(RA)的临床研究,以说明该技术的实用性。计算每个样本的雄激素和雌激素受体、PI3K、MAPK、TGFβ、Notch、NFκB、JAK-STAT1/2 和 JAK-STAT3 STP 的活性,生成由 9 个活性评分组成的 STP 活性谱 (SAP)。每种分析的免疫细胞类型,即初始/静息和免疫激活的 CD4 和 CD8 T 细胞、T 辅助细胞、B 细胞、NK 细胞、单核细胞、巨噬细胞和树突状细胞,都具有可重复的特征性 SAP,反映了细胞类型和其活动状态。临床 RA 样本分析显示全血样本中 TGFβ STP 活性增加。总之,STAP-STP技术能够定量测量先天性和适应性免疫系统的免疫细胞的功能活动状态。除了诊断应用之外,其用途还在于揭示疾病和免疫调节药物开发中的异常免疫功能。© 2024。作者。
For many diseases, including cancer, infections, and auto-immune diseases, the immune response is a major determinant of disease progression, response to therapy, and clinical outcome. Innate and adaptive immune responses are controlled by coordinated activity of different immune cell types. The functional activity state of immune cells is determined by Signal Transduction Pathways (STPs). A recently developed technology (Simultaneous Transcriptome-based Activity Profiling of Signal Transduction Pathways, STAP-STP) enables simultaneous and quantitative activity measurement of relevant STPs in immune cells based on mRNA-analysis. STAP-STP technology was used to analyze public transcriptome data of a variety of immune cell types in resting and activated functional state. In addition, a clinical study on rheumatoid arthritis (RA) was analyzed to illustrate utility of the technology. Per sample, activity of androgen and estrogen receptor, PI3K, MAPK, TGFβ, Notch, NFκB, JAK-STAT1/2, and JAK-STAT3 STPs was calculated, generating an STP activity profile (SAP) consisting of 9 activity scores. Each analyzed immune cell type, i.e. naive/resting and immune-activated CD4 + and CD8 + T cells, T helper cells, B cells, NK cells, monocytes, macrophages, and dendritic cells, had a reproducible and characteristic SAP, reflecting both cell type and its activity state. Analysis of clinical RA samples revealed increased TGFβ STP activity in whole blood samples. In conclusion, STAP-STP technology enables quantitative measurement of the functional activity state of immune cells of the innate and adaptive immune system. Aside from diagnostic applications, utility lies in unravelling abnormal immune function in disease and immunomodulatory drug development.© 2024. The Author(s).