Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Mol Med. 2023 Sep 4;29(1):117. doi: 10.1186/s10020-023-00717-3.
HMGB1, a nucleoprotein, is expressed in almost all eukaryotic cells. During cell activation and cell death, HMGB1 can function as an alarm protein (alarmin) or damage-associated molecular pattern (DAMP) and mediate early inflammatory and immune response when it is translocated to the extracellular space. The binding of extracellular HMGB1 to Toll-like receptors (TLRs), such as TLR2 and TLR4 transforms HMGB1 into a pro-inflammatory cytokine, contributing to the occurrence and development of autoimmune diseases. TLRs, which are members of a family of pattern recognition receptors, can bind to endogenous DAMPs and activate the innate immune response. Additionally, TLRs are key signaling molecules mediating the immune response and play a critical role in the host defense against pathogens and the maintenance of immune balance. HMGB1 and TLRs are reported to be upregulated in several autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, and autoimmune thyroid disease. The expression levels of HMGB1 and some TLRs are upregulated in tissues of patients with autoimmune diseases and animal models of autoimmune diseases. The suppression of HMGB1 and TLRs inhibits the progression of inflammation in animal models. Thus, HMGB1 and TLRs are indispensable biomarkers and important therapeutic targets for autoimmune diseases. This review provides comprehensive strategies for treating or preventing autoimmune diseases discovered in recent years.
高迁移率族蛋白 B1（HMGB1）是一种核蛋白，几乎存在于所有真核细胞中。在细胞激活和细胞死亡过程中，HMGB1 可作为警报蛋白（alarmin）或损伤相关分子模式（DAMP）发挥作用，当其转移到细胞外空间时，可介导早期炎症和免疫反应。细胞外 HMGB1 与 Toll 样受体（TLRs）（如 TLR2 和 TLR4）结合，将 HMGB1 转化为促炎细胞因子，促进自身免疫性疾病的发生和发展。TLRs 是模式识别受体家族的成员，可与内源性 DAMPs 结合并激活固有免疫反应。此外，TLRs 是介导免疫反应的关键信号分子，在宿主防御病原体和维持免疫平衡方面发挥着至关重要的作用。据报道，HMGB1 和 TLRs 在几种自身免疫性疾病中上调，如类风湿关节炎、系统性红斑狼疮、1 型糖尿病和自身免疫性甲状腺疾病。HMGB1 和某些 TLRs 的表达水平在自身免疫性疾病患者的组织和自身免疫性疾病动物模型中上调。抑制 HMGB1 和 TLRs 可抑制动物模型中的炎症进展。因此，HMGB1 和 TLRs 是自身免疫性疾病不可或缺的生物标志物和重要治疗靶点。本文综述了近年来发现的治疗或预防自身免疫性疾病的综合策略。
