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揭示树突状细胞中 NLRP3 炎症小体作为自身免疫、癌症和感染性疾病的潜在治疗靶点

英文原题:Unmasking the NLRP3 inflammasome in dendritic cells as a potential therapeutic target for autoimmunity, cancer, and infectious conditions.

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Unmasking the NLRP3 inflammasome in dendritic cells as a potential therapeutic target for autoimmunity, cancer, and infectious conditions.

PubMed 2024/05/06(内容时间) Life Sci Q1 · IF 6.4(JCR 2025)

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中文摘要

适当的免疫功能需要固有免疫细胞和适应性免疫细胞之间复杂的相互作用,其中树突状细胞(DCs)作为专业抗原呈递细胞,是这种协调过程中的主要参与者。DCs配备了众多模式识别受体(PRRs),例如核苷酸结合和寡聚化结构域样受体(NLRs)如NLRP3,这些受体在感知配体后会影响其活化状态的发展。NLRP3是免疫系统中抵御肿瘤和感染因子的关键组成部分,因为其激活会导致炎症小体组装,进而促使活性caspase-1形成,并刺激促炎细胞因子的成熟和释放。

但是,当NLRP3过度激活时,它在多种自身免疫性疾病的进展中发挥致病作用。因此,NLRP3的激活受到多种信号通路的严格调控,本综述对此进行了详细阐述。

此外,本研究还简要提及了NLRP3在各类不同免疫细胞亚群中的作用,因为NLRP3在调节其他免疫细胞方面发挥关键作用,这些细胞与DCs的反应相伴,并随后影响T细胞向不同T helper亚群的分化,甚至影响细胞毒性CD8 + T细胞的反应。本综述阐明了NLRP3在DCs中的功能性和治疗性作用,以及它對自身免疫性疾病发生和进展、多种肿瘤发展预防以及各种感染因子识别和清除的贡献。

此外,我们强调了NLRP3靶向在改善基于DCs的免疫治疗方法方面的潜力,以造福于患有这些疾病的患者。

展开英文摘要原文

Proper and functional immune response requires a complex interaction between innate and adaptive immune cells, which dendritic cells (DCs) are the primary actors in this coordination as professional antigen-presenting cells. DCs are armed with numerous pattern recognition receptors (PRRs) such as nucleotide-binding and oligomerization domain-like receptors (NLRs) like NLRP3, which influence the development of their activation state upon sensation of ligands.

NLRP3 is a crucial component of the immune system for protection against tumors and infectious agents, because its activation leads to the assembly of inflammasomes that cause the formation of active caspase-1 and stimulate the maturation and release of proinflammatory cytokines.

But, when NLRP3 becomes overactivated, it plays a pathogenic role in the progression of several autoimmune disorders. So, NLRP3 activation is strictly regulated by diverse signaling pathways that are mentioned in detail in this review.

Furthermore, the role of NLRP3 in all of the diverse immune cells' subsets is briefly mentioned in this study because NLRP3 plays a pivotal role in modulating other immune cells which are accompanied by DCs' responses and subsequently influence differentiation of T cells to diverse T helper subsets and even impact on cytotoxic CD8 + T cells' responses.

This review sheds light on the functional and therapeutic role of NLRP3 in DCs and its contribution to the occurrence and progression of autoimmune disorders, prevention of diverse tumors' development, and recognition and annihilation of various infectious agents.

Furthermore, we highlight NLRP3 targeting potential for improving DC-based immunotherapeutic approaches, to be used for the benefit of patients suffering from these disorders.

论文信息

作者
Alipour S、Mardi A、Shajari N、Kazemi T、Sadeghi MR、Ahmadian Heris J、Masoumi J、Baradaran B
第一作者单位
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.Iran
通讯作者单位
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: baradaranb@tbzmed.ac.ir.Iran
文献类型
综述
期刊
Life sciences2024 Jul 1
原文标识
PubMed 38710282 · DOI 10.1016/j.lfs.2024.122686