Badal Darshan, Sachdeva Naresh, Maheshwari Deep, Basak Preetam
Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
World J Diabetes. 2021 Oct 15;12(10):1655-1673. doi: 10.4239/wjd.v12.i10.1655.
During infections, nucleic acids of pathogens are also engaged in recognition several exogenous and cytosolic pattern recognition receptors, such as the toll-like receptors, retinoic acid inducible gene-I-like receptors, and nucleotide-binding and oligomerization domain-like receptors. The binding of the pathogen-derived nucleic acids to their corresponding sensors initiates certain downstream signaling cascades culminating in the release of type-I interferons (IFNs), especially IFN-α and other cytokines to induce proinflammatory responses towards invading pathogens leading to their clearance from the host. Although these sensors are hardwired to recognize pathogen associated molecular patterns, like viral and bacterial nucleic acids, under unusual physiological conditions, such as excessive cellular stress and increased apoptosis, endogenous self-nucleic acids like DNA, RNA, and mitochondrial DNA are also released. The presence of these self-nucleic acids in extranuclear compartments or extracellular spaces or their association with certain proteins sometimes leads to the failure of discriminating mechanisms of nucleic acid sensors leading to proinflammatory responses as seen in autoimmune disorders, like systemic lupus erythematosus, psoriasis and to some extent in type 1 diabetes (T1D). This review discusses the involvement of various nucleic acid sensors in autoimmunity and discusses how aberrant recognition of self-nucleic acids by their sensors activates the innate immune responses during the pathogenesis of T1D.
在感染过程中，病原体的核酸也会与几种外源性和胞质模式识别受体相互作用，如Toll样受体、视黄酸诱导基因-I样受体以及核苷酸结合寡聚化结构域样受体。病原体衍生的核酸与其相应传感器的结合会启动某些下游信号级联反应，最终导致I型干扰素（IFN），尤其是IFN-α和其他细胞因子的释放，从而诱导针对入侵病原体的促炎反应，使其从宿主体内清除。尽管这些传感器生来就用于识别病原体相关分子模式，如病毒和细菌核酸，但在异常生理条件下，如过度的细胞应激和细胞凋亡增加时，内源性自身核酸，如DNA、RNA和线粒体DNA也会释放出来。这些自身核酸存在于核外区室或细胞外空间，或它们与某些蛋白质的结合，有时会导致核酸传感器的识别机制失效，从而引发促炎反应，如在系统性红斑狼疮、银屑病等自身免疫性疾病中所见，在1型糖尿病（T1D）中也有一定程度的体现。本综述讨论了各种核酸传感器在自身免疫中的作用，并探讨了它们对自身核酸的异常识别如何在T1D发病机制中激活先天性免疫反应。
