摘要
背景:固有免疫和适应性免疫之间错综复杂的相互作用在疾病、感染和接种疫苗过程有效的免疫应答中起着关键的作用。这种作用主要由树突状细胞表达,这种专有的抗原呈递细胞具有独特的能力,能够将固有免疫转化为适应性免疫。他们能够有效的识别和吸收抗原,并迁徙到淋巴组织,激活T细胞。此外,树突状细胞具有种系编码的模式识别受体(PRR),其识别保守的病原体相关分子模式(PAMP)或危险相关分子模式(DAMP)。虽然一些PRRs 如Toll样受体(TLRs),识别细胞表面和内体/ 溶酶体区室中的PAMP和DAMP,但其他如NOD样受体(NLR)则可以作为细胞溶质传感器。通过识别PAMPs和DAMP引起的NLR激活导致命名为炎症细胞的信号多聚体蛋白复合物的组装。炎症复合物是胱天蛋白酶1的重要调节剂,其是负责将前体前IL-1β和前IL-18蛋白水解切割成其活性形式的酶。 目的:揭示炎症反应如何与成熟、迁移、抗原呈递功能和DC相关,微调适应性免疫反应的能力。 结论:几项研究表明,在危险或感染情况下,NLR和TLR协同增强DCs成熟,迁移,抗原呈递功能和适应性免疫系统激活。然而,如果没有危险情况,并且没有TLR参与,炎性体激活刺激DC上的免疫抑制谱。总的来说,从文献中可以清楚地看出,DCs中的炎症小体的活化不应该被孤立地看待,而是考虑到它与各种PPR驱动途径的互连。由于炎症性疾病参与多种炎症和免疫疾病的证据越来越多,这一信息是非常重要的,因为精确的炎症性药理学靶向可以通过微调靶向治疗导致相当的临床应用。
关键词: 佐剂,树突状细胞,炎性体,NLR,TLR,NLRP3,DAMPs
图形摘要
Current Drug Targets
Title:Inflammasome in Dendritic Cells Immunobiology: Implications to Diseases and Therapeutic Strategies
Volume: 18 Issue: 9
关键词: 佐剂,树突状细胞,炎性体,NLR,TLR,NLRP3,DAMPs
摘要: Background: An intricate interplay between innate and adaptive immune cells is crucial for an effective immune response during disease, infection and vaccination. This interplay is mainly performed by dendritic cells (DCs), which are professional antigen presenting cells with unparalleled capacity to translate innate to adaptive immunity. They effectively recognize and uptake antigens, migrate to lymphoid tissues, and activate naïve T-cells. Indeed, DCs have numerous germline encoded pattern recognition receptors (PRR) that recognize conserved pathogen associated molecular patterns (PAMPs) or danger associated molecular patterns (DAMPs). While some PRRs like Toll-like receptors (TLRs) recognize PAMPs and DAMPs at the cell surface and in endosomal/lysosomal compartments, others, such as NOD-like receptors (NLRs), act as cytosolic sensors. NLRs activation through recognition of PAMPs and DAMPs leads to the assembly of signaling multimeric protein complexes named inflammasomes. Inflammasomes are important regulators of caspase 1, the enzyme responsible for the proteolytically cleavage of precursors’ pro-IL-1β and pro-IL-18 into their active form.
Objective: To unveil how inflammasomes are related to maturation, migration, antigen presenting function and DCs ability to fine tune adaptive immune responses. Conclusion: Several studies show that in danger/infectious scenarios NLR and TLR synergize to expand DCs maturation, migration, antigen presenting function and adaptive immune system activation. However, in the absence of a danger scenario, and without TLR engagement, inflammasome activation stimulates an immunosuppressive profile on DCs. Overall, it is clear from literature that activation of the inflammasome in DCs should not be viewed in isolation but rather considering its interconnections with the various PPRdriven pathways. Due to the increasing evidences of inflammasome involvement in multiple inflammatory and immune diseases, this information is of utmost importance since precise inflammasome pharmacological targeting could lead to considerable clinical utility through fine-tuned targeted therapies.Export Options
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Cite this article as:
Inflammasome in Dendritic Cells Immunobiology: Implications to Diseases and Therapeutic Strategies, Current Drug Targets 2017; 18 (9) . https://dx.doi.org/10.2174/1389450117666160921144830
DOI https://dx.doi.org/10.2174/1389450117666160921144830 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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