ABSTRACT

Phosphatidylserine (PS) is a naturally occurring anionic phospholipid that is primarily located in the inner leaflet of eukaryotic cell membranes. The role of PS during apoptosis is one of the most studied biological functions of PS. Externalization of PS during apoptosis mediates an “eat me” signal for phagocytic uptake, leading to clearance of apoptotic cells and thus maintain self-tolerance by immunological ignorance. However, an emerging view is that PS exposure-mediated cellular uptake is not an immunologically silent event, but rather promoting an active tolerance towards self and foreign proteins. This biological property of PS has been exploited by parasites and viruses in order to evade immune surveillance of the host immune system. Further, this novel immune regulatory property of PS that results in tolerance induction can be harnessed for clinical applications, such as to treat autoimmune conditions and to reduce immunogenicity of therapeutic proteins. This review attempts to provide an overview of the biological functions of PS in the immune response and its potential therapeutic applications.

摘要

磷脂酰丝氨酸 (PS) 是一种天然存在的阴离子磷脂，主要位于真核细胞膜的内部小叶中。PS 在细胞凋亡过程中的作用是 PS 研究最多的生物学功能之一。细胞凋亡过程中 PS 的外化介导了吞噬细胞摄取的“吃我”信号，导致凋亡细胞的清除，从而通过免疫学无知保持自我耐受。然而，新出现的观点是 PS 暴露介导的细胞摄取不是免疫沉默事件，而是促进对自身和外来蛋白质的主动耐受。PS 的这种生物学特性已被寄生虫和病毒利用，以逃避宿主免疫系统的免疫监视。更远，PS 的这种导致耐受性诱导的新型免疫调节特性可用于临床应用，例如治疗自身免疫性疾病和降低治疗性蛋白质的免疫原性。本综述试图概述 PS 在免疫反应中的生物学功能及其潜在的治疗应用。