Beignon Anne-Sophie, Galeotti Caroline, Menager Mickael M, Schvartz Adrien
Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases/Infectious Diseases Models and Innovative Technologies (IMVA-HB/IDMIT), U1184, Université Paris-Saclay, INSERM, CEA, Fontenay-aux-Roses, France.
Department of Pediatric Rheumatology, Reference Center for AutoInflammatory Diseases and Amyloidosis (CEREMAIA), Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France.
Front Med (Lausanne). 2023 Jan 10;9:1085339. doi: 10.3389/fmed.2022.1085339. eCollection 2022.
Autoimmune disorders have been well characterized over the years and many pathways-but not all of them-have been found to explain their pathophysiology. Autoinflammatory disorders, on the other hand, are still hiding most of their molecular and cellular mechanisms. During the past few years, a newcomer has challenged the idea that only adaptive immunity could display memory response. Trained immunity is defined by innate immune responses that are faster and stronger to a second stimulus than to the first one, being the same or not. In response to the trained immunity inducer, and through metabolic and epigenetic changes of hematopoietic stem and progenitor cells in the bone marrow that are transmitted to their cellular progeny (peripheral trained immunity), or directly of tissue-resident cells (local innate immunity), innate cells responsiveness and functions upon stimulation are improved in the long-term. Innate immunity can be beneficial, but it could also be detrimental when maladaptive. Here, we discuss how trained immunity could contribute to the physiopathology of autoimmune and autoinflammatory diseases.
多年来,自身免疫性疾病已得到充分的表征,并且已经发现了许多(但并非全部)途径来解释其病理生理学。另一方面,自身炎症性疾病仍隐藏着其大部分分子和细胞机制。在过去几年中,一个新出现的概念挑战了只有适应性免疫才能表现出记忆反应的观点。训练有素的免疫是由先天免疫反应定义的,即对第二次刺激的反应比对第一次刺激更快、更强,无论第一次和第二次刺激是否相同。响应训练有素的免疫诱导剂,并通过骨髓中造血干细胞和祖细胞的代谢和表观遗传变化传递给它们的细胞后代(外周训练有素的免疫),或直接作用于组织驻留细胞(局部先天免疫),长期来看,先天细胞在受到刺激时的反应性和功能会得到改善。先天免疫可能是有益的,但当出现适应不良时也可能是有害的。在这里,我们讨论训练有素的免疫如何可能导致自身免疫性疾病和自身炎症性疾病病理生理过程的发生。