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The quest for faithful in vitro models of human dendritic cells types.
Molecular Immunology ( IF 3.6 ) Pub Date : 2020-05-12 , DOI: 10.1016/j.molimm.2020.04.018
Xin-Long Luo 1 , Marc Dalod 1
Affiliation  

Dendritic cells (DCs) are mononuclear phagocytes that are specialized in the induction and functional polarization of effector lymphocytes, thus orchestrating immune defenses against infections and cancer. The population of DC encompasses distinct cell types that vary in their efficacy for complementary functions and are thus likely involved in defending the body against different threats. Plasmacytoid DCs specialize in the production of high levels of the antiviral cytokines type I interferons. Type 1 conventional DCs (cDC1s) excel in the activation of cytotoxic CD8+ T cells (CTLs) which are critical for defense against cancer and infections by intracellular pathogens. Type 2 conventional DCs (cDC2s) prime helper CD4+ T cells for the production of type 2 cytokines underpinning immune defenses against worms or of IL-17 promoting control of infections by extracellular bacteria or fungi. Hence, clinically manipulating the development and functions of DC types could have a major impact for improving treatments against many diseases. However, the rarity and fragility of human DC types is impeding advancement towards this goal. To overcome this roadblock, major efforts are ongoing to generate in vitro large numbers of distinct human DC types. We review here the current state of this research field, emphasizing recent breakthrough and proposing future priorities. We also pinpoint the necessity to develop a consensus nomenclature and rigorous methodologies to ensure proper identification and characterization of human DC types. Finally, we elaborate on how faithful in vitro models of human DC types can accelerate our understanding of the biology of these cells and the engineering of next generation vaccines or immunotherapies against viral infections or cancer.

中文翻译:

对人类树突状细胞类型的体外模型的忠实追求。

树突状细胞(DC)是单核吞噬细胞,专门作用于效应淋巴细胞的诱导和功能极化,从而协调针对感染和癌症的免疫防御。DC群体包含不同的细胞类型,这些细胞的互补功能功效不同,因此很可能参与了防御各种威胁的机体。浆细胞样DC专门生产高水平的I型抗病毒细胞因子干扰素。1型常规DC(cDC1s)在激活细胞毒性CD8 + T细胞(CTL)方面表现出色,这对于防御癌症和细胞内病原体感染至关重要。2型常规DC(cDC2)主要辅助CD4 + T细胞用于产生2型细胞因子,从而增强了针对蠕虫或IL-17的免疫防御能力,从而促进了对细胞外细菌或真菌感染的控制。因此,临床上控制DC类型的发展和功能可能会对改善针对多种疾病的治疗产生重大影响。但是,人类DC类型的稀有性和脆弱性阻碍了朝着这个目标前进。为了克服这一障碍,正在进行大量努力以在体外产生大量不同的人类DC类型。我们在这里回顾该研究领域的现状,强调近期的突破并提出未来的重点。我们还指出了发展共识性术语和严格方法的必要性,以确保正确识别和表征人类DC类型。最后,我们详细阐述了人类DC类型的体外模型如何能加快我们对这些细胞的生物学以及下一代针对病毒感染或癌症的疫苗或免疫疗法的工程设计的理解。
更新日期:2020-05-13
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