CNRS-UMR 5164, ImmunoConcEpT, Bordeaux University, Bordeaux, France.
Department of Pathology, New York University Grossman School of Medicine, New York, NY, United States.
Front Immunol. 2021 Feb 26;12:629922. doi: 10.3389/fimmu.2021.629922. eCollection 2021.
Detection of microbial nucleic acids by the innate immune system is mediated by numerous intracellular nucleic acids sensors. Upon the detection of nucleic acids these sensors induce the production of inflammatory cytokines, and thus play a crucial role in the activation of anti-microbial immunity. In addition to microbial genetic material, nucleic acid sensors can also recognize self-nucleic acids exposed extracellularly during turn-over of cells, inefficient efferocytosis, or intracellularly upon mislocalization. Safeguard mechanisms have evolved to dispose of such self-nucleic acids to impede the development of autoinflammatory and autoimmune responses. These safeguard mechanisms involve nucleases that are either specific to DNA (DNases) or RNA (RNases) as well as nucleic acid editing enzymes, whose biochemical properties, expression profiles, functions and mechanisms of action will be detailed in this review. Fully elucidating the role of these enzymes in degrading and/or processing of self-nucleic acids to thwart their immunostimulatory potential is of utmost importance to develop novel therapeutic strategies for patients affected by inflammatory and autoimmune diseases.
先天免疫系统通过多种细胞内核酸传感器来检测微生物核酸。这些传感器在检测到核酸后会诱导炎症细胞因子的产生，因此在激活抗微生物免疫中起着至关重要的作用。除了微生物的遗传物质外，核酸传感器还可以识别细胞更替、吞噬作用效率低下或细胞内定位错误时暴露于细胞外的自身核酸。已经进化出保护机制来处理这些自身核酸，以阻止自身炎症和自身免疫反应的发展。这些保护机制涉及到专门针对 DNA（DNases）或 RNA（RNases）的核酸酶以及核酸编辑酶，本综述将详细介绍它们的生化特性、表达谱、功能和作用机制。充分阐明这些酶在降解和/或加工自身核酸以阻止其免疫刺激潜力方面的作用，对于为受炎症和自身免疫性疾病影响的患者开发新的治疗策略至关重要。
