Divisão de Reumatologia, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
Divisão de Imunologia, Laboratório Fleury, São Paulo, SP, Brasil.
Braz J Med Biol Res. 2024 Jun 17;57:e13225. doi: 10.1590/1414-431X2024e13225. eCollection 2024.
Innate immune system activation is crucial in the inflammatory response, but uncontrolled activation can lead to autoimmune diseases. Cellular exhaustion and senescence are two processes that contribute to innate immune tolerance breakdown. Exhausted immune cells are unable to respond adequately to specific antigens or stimuli, while senescent cells have impaired DNA replication and metabolic changes. These processes can impair immune system function and disrupt homeostasis, leading to the emergence of autoimmunity. However, the influence of innate immune exhaustion and senescence on autoimmune disorders is not well understood. This review aims to describe the current findings on the role of innate immune exhaustion and senescence in autoimmunity, focusing on the cellular and molecular changes involved in each process. Specifically, the article explores the markers and pathways associated with immune exhaustion, such as PD-1 and TIM-3, and senescence, including Β-galactosidase (β-GAL), lamin B1, and p16ink4a, and their impact on autoimmune diseases, namely type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, and immune-mediated myopathies. Understanding the mechanisms underlying innate immune exhaustion and senescence in autoimmunity may provide insights for the development of novel therapeutic strategies.
先天免疫系统的激活在炎症反应中至关重要，但过度激活可能导致自身免疫性疾病。细胞耗竭和衰老（senescence）是导致先天免疫耐受破坏的两个过程。耗竭的免疫细胞无法对特定抗原或刺激物做出充分反应，而衰老的细胞则存在 DNA 复制受损和代谢变化。这些过程可能会损害免疫系统功能并破坏体内平衡，导致自身免疫的出现。然而，先天免疫耗竭和衰老对自身免疫性疾病的影响尚不清楚。本综述旨在描述先天免疫耗竭和衰老在自身免疫中的作用的现有研究结果，重点介绍每个过程中涉及的细胞和分子变化。具体而言，本文探讨了与免疫耗竭相关的标志物和途径，如 PD-1 和 TIM-3，以及与衰老相关的标志物和途径，包括 Β-半乳糖苷酶（β-GAL）、核纤层蛋白 B1 和 p16ink4a，并探讨了它们对自身免疫性疾病（如 1 型糖尿病、类风湿关节炎、系统性红斑狼疮和免疫介导的肌病）的影响。了解自身免疫中先天免疫耗竭和衰老的机制可能为开发新的治疗策略提供思路。
