Deretic Vojo
Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131-001, USA.
Dig Dis. 2009;27(3):246-51. doi: 10.1159/000228557. Epub 2009 Sep 24.
Autophagy is a fundamental biological process that endows eukaryotic cells with the ability to autodigest portions of their own cytoplasm. Autophagy plays roles in aging, development, neurodegeneration, cancer and immunity. The immunological role of autophagy was first recognized for the ability of autophagy to sanitize the cellular interior by killing intracellular microbes and, indirectly, by the adaptations that successful intracellular pathogens have evolved to protect themselves from autophagy. Since then, the repertoire of autophagy functions in immunity has been vastly expanded to include numerous intersections of regulatory and effector nature with innate and adaptive immunity. Autophagy acts both as an effector and a regulator of pattern recognition receptors, it supports MHC II presentation of cytosolic (self and microbial) antigens, it shapes central tolerance via thymic selection of the T cell repertoire, is an effector of Th1/Th2 polarization, affects homeostasis of T, B, and specialized immune cells such as Paneth cells, and - when defective - can be a contributing factor to chronic inflammatory conditions in human populations such as Crohn's disease.
自噬是一种基本的生物学过程,它赋予真核细胞自我消化自身部分细胞质的能力。自噬在衰老、发育、神经退行性变、癌症和免疫中发挥作用。自噬的免疫作用最初是因其能够通过杀死细胞内微生物来净化细胞内部,以及间接通过成功的细胞内病原体进化出的保护自身免受自噬的适应性机制而被认识到的。从那时起,自噬在免疫中的功能范围得到了极大的扩展,包括与固有免疫和适应性免疫在调节和效应性质方面的众多交叉。自噬既是模式识别受体的效应器又是调节因子,它支持MHC II对胞质(自身和微生物)抗原的呈递,它通过胸腺对T细胞库的选择塑造中枢耐受,是Th1/Th2极化的效应器,影响T细胞、B细胞和诸如潘氏细胞等特殊免疫细胞的稳态,并且——当功能缺陷时——可能是人类群体中慢性炎症性疾病如克罗恩病的一个促成因素。