Laboratorio de Imunogenetica, Departamento de Imunologia, Instituto de Ciencias Biomedicas/ICB, Universidade de Sao Paulo/USP, Sao Paulo, SP, Brazil.
Eur J Hum Genet. 2020 Oct;28(10):1307-1321. doi: 10.1038/s41431-020-0631-y. Epub 2020 Jun 4.
The inflammasome is a cytoplasmic multiprotein complex responsible for the activation of inflammatory caspases (caspase-1, -4, and -5) in response to pathogen- and/or damage-associated molecular patterns or to homeostasis-altering molecular pathways, and for the consequent release of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-18. Taking in account the complexity of inflammasome activation and that several regulatory steps are involved in maintaining its physiologic role in homeostasis and innate immune response, it does not surprise that several genetic variants in inflammasome components have been associated with common pathologies in the general population, such as autoimmune disorders, cardiovascular diseases, obesity and associated metabolic syndrome, neurodegenerative diseases, and cancer. Moreover, the susceptibility to infectious agents and/or to develop severe complications during infections also has been related to inflammasome genetics. In this work, we revised genetic association studies about polymorphisms of main inflammasome genes in sterile as well as infectious diseases, trying to depict the genetic contribution of inflammasome in disease pathogenesis.
炎症小体是一种细胞质多蛋白复合物，负责在病原体和/或损伤相关分子模式或改变内稳态的分子途径的刺激下激活炎症半胱天冬酶（caspase-1、-4 和 -5），并随之释放促炎细胞因子白细胞介素（IL）-1β和 IL-18。考虑到炎症小体激活的复杂性，以及几个调节步骤涉及到维持其在维持内稳态和先天免疫反应中的生理作用，因此炎症小体成分的几个遗传变异与普通人群中的常见病理有关，如自身免疫性疾病、心血管疾病、肥胖症和相关代谢综合征、神经退行性疾病和癌症，这并不奇怪。此外，对感染剂的易感性和/或在感染过程中发展为严重并发症也与炎症小体遗传学有关。在这项工作中，我们综述了炎症小体主要基因的多态性在非感染性和感染性疾病中的遗传相关性研究，试图描述炎症小体在疾病发病机制中的遗传贡献。
