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B链关节蛋白诱导树突状细胞成熟,并驱动I型辅助性T细胞和细胞毒性T细胞活化。

Articulatin B chain induced dendritic cells maturation and driven type I T helper cells and cytotoxic T cells activation.

作者信息

Lu Tzu-Li, Sher Yuh-Pyng, Chen Hui-Chen, Cheng Wei-Chung, Hsu Ling-Heng, Lee Chen-Chen

机构信息

Department of Medical Laboratory Science and Biotechnology, Taichung, Taiwan.

Graduate Institute of Biomedical Sciences, Taichung, Taiwan.

出版信息

Life Sci. 2022 Aug 1;302:120635. doi: 10.1016/j.lfs.2022.120635. Epub 2022 May 13.

DOI:10.1016/j.lfs.2022.120635
PMID:35569571
Abstract

AIMS

Articulatin (AT), purified from the Chinese mistletoe (Viscum articulatum), belongs to the family of type II ribosome-inactivating proteins (RIPs) that contain two subunits, the A and B chains. The B chain of AT is believed to function by means of interacting with the galactose moiety of glycoproteins or glycolipids on the cell membrane and is internalized into cells through endocytosis. In the study, we aim to investigate the immunomodulatory effects of recombinant articulatin B chain (rATB) on mouse bone marrow-derived dendritic cells (BM-DCs).

MAIN METHODS

Detection of surface markers expression on BM-DCs by flow cytometry. Analysis of RNA and protein expression by RNAseq and Western blotting assays. Assessment of the adaptive immune responses using an in vivo mouse model.

KEY FINDING

Our study presents novel results showing the activation of mouse BM-DCs by rATB, which leads to the induction of CD80, CD86, and MHC II expression as well as primed type I CD4 T cell differentiation and CD8 T cell activation. RNAseq and Western blotting assays revealed rATB-induced BM-DC activation to be dependent on the MAPK and NF-κB signaling pathways. In a mouse model, rATB was observed to have adjuvant effects that induced an antigen-specific Th1 immune response.

SIGNIFICANCE

Based on in vitro and in vivo assays, this study shows rATB acting as a potential adjuvant that induces BM-DC activation and antigen-specific Th1 related immune response. rATB might have potential applicability in the development of vaccines against pathogens and tumors.

摘要

目的

从中国槲寄生(Articulatum槲寄生)中纯化得到的Articulatin(AT)属于II型核糖体失活蛋白(RIPs)家族,其包含A和B两条亚基。AT的B链被认为通过与细胞膜上糖蛋白或糖脂的半乳糖部分相互作用来发挥功能,并通过内吞作用内化进入细胞。在本研究中,我们旨在探究重组Articulatin B链(rATB)对小鼠骨髓来源树突状细胞(BM-DCs)的免疫调节作用。

主要方法

通过流式细胞术检测BM-DCs表面标志物的表达。采用RNAseq和蛋白质免疫印迹分析RNA和蛋白质表达。利用体内小鼠模型评估适应性免疫反应。

关键发现

我们的研究呈现了新的结果,显示rATB可激活小鼠BM-DCs,这导致CD80、CD86和MHC II表达的诱导以及I型CD4 T细胞分化和CD8 T细胞激活的启动。RNAseq和蛋白质免疫印迹分析显示,rATB诱导的BM-DC激活依赖于MAPK和NF-κB信号通路。在小鼠模型中,观察到rATB具有诱导抗原特异性Th1免疫反应的佐剂作用。

意义

基于体外和体内试验,本研究表明rATB作为一种潜在佐剂可诱导BM-DC激活和抗原特异性Th1相关免疫反应。rATB在针对病原体和肿瘤的疫苗开发中可能具有潜在的适用性。

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