HMGB1 and Toll-like receptors: potential therapeutic targets in autoimmune diseases

Molecular Medicine

Review

Ying Sun¹  Xiaoguang Shi¹  Wenxuan Ren¹  Xichang Wang¹  Lei Zhao² 

[1] Department of Endocrinology, Shengjing Hospital of China Medical University, 110001, Shenyang, Liaoning, China;Department of Laboratory Medicine, The First Hospital of China Medical University, 110001, Shenyang, Liaoning, China;

关键词: HMGB1;    Toll-like receptors;    Autoimmune diseases;    Rheumatoid arthritis;    Systemic lupus erythematosus;    Autoimmune thyroid disease;   

DOI  :  10.1186/s10020-023-00717-3

 received in 2023-05-28, accepted in 2023-08-14,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Feinstein Institute for Medical Research 2023

【 图 表 】

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