The Therapeutic and Pathogenic Role of Autophagy in Autoimmune Diseases.

The Therapeutic and Pathogenic Role of Autophagy in Autoimmune Diseases.
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自噬在自身免疫性疾病中的治疗和致病作用

DOI:
10.3389/fimmu.2018.01512
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发表时间:
2018
影响因子:
7.3
通讯作者:
Lu Q
Lu Q
中科院分区:
医学2区
文献类型:
--
作者:
Yin H;Wu H;Chen Y;Zhang J;Zheng M;Chen G;Li L;Lu Q

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自噬是一种复杂的细胞机制,通过降解衰老的、有缺陷的亚细胞细胞器、感染剂和错误折叠的蛋白质来维持细胞和组织的动态平衡和完整性。越来越多的证据表明,自噬参与了许多免疫过程,如清除细胞内细菌、细胞因子的产生、自身抗原的提呈和淋巴细胞的存活,这表明自噬在先天性和获得性免疫反应中发挥着明显而重要的作用。事实上,在全基因组相关研究中,自噬相关基因多态性被认为与几种自身免疫性和炎症性疾病的发病机制有关,如系统性红斑狼疮、银屑病、类风湿性关节炎、炎症性肠病和多发性硬化症。此外,有条件地敲除小鼠的自噬相关基因,通过降低炎症细胞因子和自身反应性免疫细胞的水平,对几种自体免疫性疾病模型显示了治疗效果。然而,自噬的抑制通过促进炎性细胞因子的产生而加速了某些炎症性和自身免疫性疾病的进展。因此,本文将对自噬在免疫调节中的研究现状进行综述,并讨论自噬在自身免疫性疾病中的治疗和致病作用,以拓宽我们对自身免疫性疾病发病机制的认识,并为自噬介导的治疗提供帮助。
Autophagy is a complicated cellular mechanism that maintains cellular and tissue homeostasis and integrity via degradation of senescent, defective subcellular organelles, infectious agents, and misfolded proteins. Accumulating evidence has shown that autophagy is involved in numerous immune processes, such as removal of intracellular bacteria, cytokine production, autoantigen presentation, and survival of lymphocytes, indicating an apparent and important role in innate and adaptive immune responses. Indeed, in genome-wide association studies, autophagy-related gene polymorphisms have been suggested to be associated with the pathogenesis of several autoimmune and inflammatory disorders, such as systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. In addition, conditional knockdown of autophagy-related genes in mice displayed therapeutic effects on several autoimmune disease models by reducing levels of inflammatory cytokines and autoreactive immune cells. However, the inhibition of autophagy accelerates the progress of some inflammatory and autoimmune diseases via promotion of inflammatory cytokine production. Therefore, this review will summarize the current knowledge of autophagy in immune regulation and discuss the therapeutic and pathogenic role of autophagy in autoimmune diseases to broaden our understanding of the etiopathogenesis of autoimmune diseases and shed light on autophagy-mediated therapies.
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