Cheng Siqi, Cui Lingyue, Chen Jingyi, Xiu Qianwei, Si Rujia, Yang Xiaoguang, Shi Ying
Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin, P.R. China.
Clinical Medical College of Jilin University, Changchun, Jilin, P.R. China.
Expert Rev Mol Med. 2025 Jun 30;27:e24. doi: 10.1017/erm.2025.10009.
SIGIRR, also known as the single immunoglobulin interleukin-1 receptor (IL-1R)-related molecule, is a member of the IL-1 receptor superfamily and is believed to play a pivotal role in inflammation and anti-inflammatory regulation within the body. Studies have shown that SIGIRR expression is associated with autoimmunity, inflammatory disorders, graft rejection, viral infection, thrombosis and tumour progression. Due to its unique structure and function, SIGIRR is commonly referred to as an 'orphan receptor', with IL-37 being the only confirmed ligand molecule for SIGIRR to date. The primary mechanism through which SIGIRR exerts its anti-inflammatory regulatory effect involves the negative modulation of the Toll-like receptor-IL-1R (TLR-IL-1R) signalling pathway. TLR-IL-1R signalling plays critical roles in immune responses triggered by microbial invasion and alterations in the tumour immune microenvironment. This article provides an overview of research findings on SIGIRR as an orphan receptor and its regulatory role in maintaining a delicate balance between natural immune activation and uncontrolled inflammatory processes under pathological conditions.
信号抑制因子（SIGIRR），也被称为单免疫球蛋白白细胞介素-1受体（IL-1R）相关分子，是IL-1受体超家族的成员，被认为在体内炎症和抗炎调节中起关键作用。研究表明，SIGIRR的表达与自身免疫、炎症性疾病、移植排斥、病毒感染、血栓形成和肿瘤进展有关。由于其独特的结构和功能，SIGIRR通常被称为“孤儿受体”，白细胞介素-37（IL-37）是迄今为止唯一被证实的SIGIRR配体分子。SIGIRR发挥其抗炎调节作用的主要机制涉及对Toll样受体-IL-1受体（TLR-IL-1R）信号通路的负调节。TLR-IL-1R信号在微生物入侵引发的免疫反应以及肿瘤免疫微环境的改变中起关键作用。本文概述了关于SIGIRR作为孤儿受体的研究结果及其在病理条件下维持天然免疫激活与不受控制的炎症过程之间微妙平衡的调节作用。
