Cacciapaglia F, Spadaccio C, Chello M, Gigante A, Coccia R, Afeltra A, Amoroso A
Department of Clinical Medicine, Immunology e Rheumatology, Campus Bio-Medico University of Rome, Italy.
Eur Rev Med Pharmacol Sci. 2009 Jan-Feb;13(1):23-40.
Apoptosis is a programmed cell death that represents a normal component of the development, differentiation and health of multicellular organisms leading to an adequate cellular turnover and homeostasis. In autoimmune diseases, the immune system recognizes various autoantigens causing damage in target organs. Dead cells represent an important source of autoantigens that, in particular conditions, can represent a stimulus for an autoimmune response. A large number of studies reported the impairment of the apoptosis regulatory mechanisms in immune cells as a pivotal element in the pathogenesis and evolution of autoimmune disorders. Several pathogenetic pathways have been claimed to account for autoimmunity development during apoptotic processes. In fact, interestingly abnormalities potentially leading to immune disorders have been described as occurring in each step involved in apoptosis, from the very beginning to the post death phenomena. In this extent we propose a systematic review of the molecular mechanisms strictly leading to apoptosis with particular interest to their alterations, potentially causing tissue specific and/or systemic autoimmunity.
细胞凋亡是一种程序性细胞死亡,是多细胞生物发育、分化和健康的正常组成部分,可实现适当的细胞更新和内环境稳定。在自身免疫性疾病中,免疫系统识别各种自身抗原,导致靶器官受损。死亡细胞是自身抗原的重要来源,在特定条件下,可成为自身免疫反应的刺激因素。大量研究报告称,免疫细胞中凋亡调节机制的损害是自身免疫性疾病发病机制和演变的关键因素。有几种致病途径被认为与凋亡过程中自身免疫的发展有关。事实上,有趣的是,从凋亡开始到死亡后现象的每一步都描述了可能导致免疫紊乱的异常情况。在此范围内,我们建议对严格导致细胞凋亡的分子机制进行系统综述,特别关注其改变,这些改变可能导致组织特异性和/或全身性自身免疫。