MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China.
Adv Exp Med Biol. 2019;1206:635-665. doi: 10.1007/978-981-15-0602-4_28.
The immune system plays a critical role in defense against invading pathogens, and its function must be strictly controlled to maintain intracellular homeostasis. Once suffering microbial invasion or receiving danger signals, the immune system initiates the responses timely. After the threat removal, the immune system should be shut down to avoid the harm caused by excessive immune activation. Additionally, the immune system needs to be internally adjusted so that it does not respond to self-antigens to avoid autoimmune diseases. The states of nonresponse in immunity are termed as immune tolerance. Numerous studies indicated that macroautophagy (hereafter named as autophagy) is involved in T cells and B cells related immune tolerance. Recently, more and more researches demonstrated that autophagy is not only capable of nonselective degradation of cellular macromolecular components but also responsible for sorting and transporting autophagic substrates through a group of cargo receptors for selective degradation, which is called as selective autophagy. Recent studies indicated that selective autophagy can effectively regulate the immune tolerance and avoid over-activation of immune response by targeting multiple receptors and effectors of immune cells. In this chapter, we will focus on how autophagy participates explicitly in the adaptive and innate immune tolerance.
免疫系统在抵御入侵病原体方面起着至关重要的作用,其功能必须受到严格控制以维持细胞内的稳态。一旦遭受微生物入侵或接收到危险信号,免疫系统就会及时启动反应。在威胁消除后,免疫系统应该关闭以避免过度免疫激活造成的伤害。此外,免疫系统需要内部调整,以免对自身抗原产生反应,从而避免自身免疫性疾病。免疫无反应的状态被称为免疫耐受。大量研究表明,巨自噬(以下简称自噬)参与了 T 细胞和 B 细胞相关的免疫耐受。最近,越来越多的研究表明,自噬不仅能够非选择性地降解细胞内的大分子成分,还能够通过一组货物受体对自噬底物进行分拣和运输进行选择性降解,这被称为选择性自噬。最近的研究表明,选择性自噬可以通过靶向免疫细胞的多种受体和效应物,有效地调节免疫耐受,避免免疫反应过度激活。在本章中,我们将重点讨论自噬如何通过靶向免疫细胞的多种受体和效应物,明确参与适应性和固有免疫耐受。