Department of Rheumatology and Clinical Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Nat Rev Rheumatol. 2023 Oct;19(10):627-639. doi: 10.1038/s41584-023-01009-0. Epub 2023 Sep 6.
The concept of immunological memory was demonstrated in antiquity when protection against re-exposure to pathogens was observed during the plague of Athens. Immunological memory has been linked with the adaptive features of T and B cells; however, in the past decade, evidence has demonstrated that innate immune cells can exhibit memory, a phenomenon called 'innate immune memory' or 'trained immunity'. Innate immune memory is currently being defined and is transforming our understanding of chronic inflammation and autoimmunity. In this Review, we provide an up-to-date overview of the memory-like features of innate immune cells in inflammatory arthritis and the crosstalk between chronic inflammatory milieu and cell reprogramming. Aberrant pro-inflammatory signalling, including cytokines, regulates the metabolic and epigenetic reprogramming of haematopoietic progenitors, leading to exacerbated inflammatory responses and osteoclast differentiation, in turn leading to bone destruction. Moreover, imprinted memory on mature cells including terminally differentiated osteoclasts alters responsiveness to therapies and modifies disease outcomes, commonly manifested by persistent inflammatory flares and relapse following medication withdrawal.
免疫记忆的概念在古代就已经得到证实，当时在雅典鼠疫期间观察到了针对再次接触病原体的保护作用。免疫记忆与 T 细胞和 B 细胞的适应性特征有关；然而，在过去十年中，有证据表明先天免疫细胞可以表现出记忆，这一现象被称为“先天免疫记忆”或“训练免疫”。目前正在对先天免疫记忆进行定义，并正在改变我们对慢性炎症和自身免疫的理解。在这篇综述中，我们提供了关于炎症性关节炎中先天免疫细胞的记忆样特征以及慢性炎症环境与细胞重编程之间相互作用的最新概述。异常的促炎信号，包括细胞因子，调节造血祖细胞的代谢和表观遗传重编程，导致炎症反应和破骨细胞分化加剧，进而导致骨破坏。此外，包括终末分化的破骨细胞在内的成熟细胞上的印记记忆改变了对治疗的反应性，并改变了疾病结果，通常表现为停药后持续的炎症发作和复发。
