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Role of nucleic acid sensing in the pathogenesis of type 1 diabetes

World Journal of Diabetes 2021年第10期12卷 1655-1673页

作者： Darshan Badal Naresh Sachdeva Deep Maheshwari Preetam Basak Department of Pediatrics Post Graduate Institute of Medical Education and ResearchChandigarh 160012India Department of Endocrinology Post Graduate Institute of Medical Education and ResearchChandigarh 160012India

During infections,nucleic acids of pathogens are also engaged in recognition via 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 *** 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-αand other cytokines to induce proinflammatory responses towards invading pathogens leading to their clearance from the *** 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 *** 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.

关键词： nucleic acid sensing Type 1 diabetes Pattern recognition receptors nucleic acid receptors Type 1 interferon Beta cells

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