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参与树突状细胞生物学功能的信号通路及其对疾病治疗的意义。

Signaling pathways involved in the biological functions of dendritic cells and their implications for disease treatment.

作者信息

Cheng Hao, Chen Wenjing, Lin Yubin, Zhang Jianan, Song Xiaoshuang, Zhang Dunfang

机构信息

Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

出版信息

Mol Biomed. 2023 May 15;4(1):15. doi: 10.1186/s43556-023-00125-3.

Abstract

The ability of dendritic cells (DCs) to initiate and regulate adaptive immune responses is fundamental for maintaining immune homeostasis upon exposure to self or foreign antigens. The immune regulatory function of DCs is strictly controlled by their distribution as well as by cytokines, chemokines, and transcriptional programming. These factors work in conjunction to determine whether DCs exert an immunosuppressive or immune-activating function. Therefore, understanding the molecular signals involved in DC-dependent immunoregulation is crucial in providing insight into the generation of organismal immunity and revealing potential clinical applications of DCs. Considering the many breakthroughs in DC research in recent years, in this review we focused on three basic lines of research directly related to the biological functions of DCs and summarized new immunotherapeutic strategies involving DCs. First, we reviewed recent findings on DC subsets and identified lineage-restricted transcription factors that guide the development of different DC subsets. Second, we discussed the recognition and processing of antigens by DCs through pattern recognition receptors, endogenous/exogenous pathways, and the presentation of antigens through peptide/major histocompatibility complexes. Third, we reviewed how interactions between DCs and T cells coordinate immune homeostasis in vivo via multiple pathways. Finally, we summarized the application of DC-based immunotherapy for autoimmune diseases and tumors and highlighted potential research prospects for immunotherapy that targets DCs. This review provides a useful resource to better understand the immunomodulatory signals involved in different subsets of DCs and the manipulation of these immune signals can facilitate DC-based immunotherapy.

摘要

树突状细胞(DCs)启动和调节适应性免疫反应的能力对于在接触自身或外来抗原时维持免疫稳态至关重要。DCs的免疫调节功能受到其分布以及细胞因子、趋化因子和转录程序的严格控制。这些因素共同作用,以确定DCs发挥免疫抑制还是免疫激活功能。因此,了解DC依赖性免疫调节中涉及的分子信号对于深入了解机体免疫的产生以及揭示DCs的潜在临床应用至关重要。考虑到近年来DC研究的诸多突破,在本综述中,我们重点关注了与DC生物学功能直接相关的三个基础研究方向,并总结了涉及DC的新免疫治疗策略。首先,我们回顾了DC亚群的最新研究结果,并确定了指导不同DC亚群发育的谱系限制性转录因子。其次,我们讨论了DC通过模式识别受体、内源性/外源性途径对抗原的识别和处理,以及通过肽/主要组织相容性复合体进行抗原呈递。第三,我们回顾了DC与T细胞之间的相互作用如何通过多种途径在体内协调免疫稳态。最后,我们总结了基于DC的免疫疗法在自身免疫性疾病和肿瘤中的应用,并强调了针对DC的免疫疗法的潜在研究前景。本综述为更好地理解不同DC亚群中涉及的免疫调节信号提供了有用的资源,并且对这些免疫信号的操控可以促进基于DC的免疫疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/10183384/ae20123b51e5/43556_2023_125_Fig1_HTML.jpg

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