Experimental and Molecular Immunology and Neurogenetics Laboratory (INEM), Centre National de la Recherche Scientifique (CNRS), UMR7355 and University of Orleans, Orleans, France.
Front Immunol. 2021 Oct 1;12:753789. doi: 10.3389/fimmu.2021.753789. eCollection 2021.
Innate immunity is regulated by a broad set of evolutionary conserved receptors to finely probe the local environment and maintain host integrity. Besides pathogen recognition through conserved motifs, several of these receptors also sense aberrant or misplaced self-molecules as a sign of perturbed homeostasis. Among them, self-nucleic acid sensing by the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway alerts on the presence of both exogenous and endogenous DNA in the cytoplasm. We review recent literature demonstrating that self-nucleic acid detection through the STING pathway is central to numerous processes, from cell physiology to sterile injury, auto-immunity and cancer. We address the role of STING in autoimmune diseases linked to dysfunctional DNAse or related to mutations in DNA sensing pathways. We expose the role of the cGAS/STING pathway in inflammatory diseases, neurodegenerative conditions and cancer. Connections between STING in various cell processes including autophagy and cell death are developed. Finally, we review proposed mechanisms to explain the sources of cytoplasmic DNA.
先天免疫受广泛的进化保守受体调节，以精细探测局部环境并维持宿主完整性。除了通过保守基序识别病原体外，这些受体中的一些还能感知异常或错位的自身分子，作为体内平衡失调的标志。其中，环状 GMP-AMP 合酶 (cGAS)/干扰素基因刺激物 (STING) 途径通过自我核酸感应，提示细胞质中外源和内源性 DNA 的存在。我们回顾了最近的文献，证明通过 STING 途径进行自我核酸检测对于从细胞生理学到无菌损伤、自身免疫和癌症等多种过程至关重要。我们讨论了 STING 在与 DNA 酶功能障碍相关或与 DNA 感应途径突变相关的自身免疫性疾病中的作用。我们揭示了 cGAS/STING 途径在炎症性疾病、神经退行性疾病和癌症中的作用。还探讨了 STING 在包括自噬和细胞死亡在内的各种细胞过程中的作用。最后，我们综述了用于解释细胞质 DNA 来源的拟议机制。
