IL-37在类风湿关节炎中作用机制的研究进展

Research progress of mechanism of IL-37 in rheumatoid arthritis

类风湿关节炎(rheumatoid arthritis,RA)是一种慢性进行性的自身免疫病,其发病机制尚未明确。在RA发生与发展过程中,细胞因子起到了重要作用。近年来针对细胞因子参与自身免疫病的研究发现,作为白细胞介素-1(interleukin-1,IL-1)家族的新成员,IL-37能够通过胞外与膜受体结合、胞内形成复合物2种方式参与调控信号通路,发挥其抗炎作用。研究表明,IL-37在健康人群体内的表达水平极低,在RA患者体内则过表达;且在RA患者血清中,IL-37水平与肿瘤坏死因子α、IL-6、IL-1α等促炎因子水平,C反应蛋白水平以及疾病活动分数28评分等呈正相关。然而,给予IL-37可以缓解胶原诱导的关节炎小鼠的炎症及病理症状,继而表明IL-37可能以负反馈的方式在RA中起着抑制炎症的作用,具体抗炎机制可能与SMAD家族成员3、核因子κB等信号通路有关。该文就IL-37的结构与表达、受体及其信号通路、功能及其在RA中的作用机制进行综述,为IL-37及RA的后续研究提供思路与参考。

Rheumatoid arthritis(RA) is a chronic progressive autoimmune disorder, the mechanism of which is not clear yet. Cytokines play a key role in the pathogenesis of RA. Recent studies on cytokine involvement in autoimmune diseases have found that, as a new member of interleukin-1(IL-1) family, IL-37 can participate in the regulation of signaling pathway and play its anti-inflammatory role by extracellular binding to membrane receptor and intracellular complex formation. Studies have shown that the expression level of IL-37 in healthy people is extremely low and overexpressed in RA patients, and the serum level of IL-37 in RA patients is positively correlated with the level of pro-inflammation cytokines such as tumor necrosis factor-α(TNF-α), IL-6 and IL-1α, the level of C reactive protein and 28-joint disease activity score(DAS28). However, IL-37 treatment can alleviate the inflammation and pathological symptoms of collagen-induced arthritis(CIA) mice, which indicates that IL-37 has anti-inflammatory effect via negative feedback. The specific anti-inflammatory mechanism may be related to mothers against decapentaplegic homolog 3(SMAD3) pathway and nuclear factor kappa-B(NF-κB) pathway. This article reviews the structure and expression of IL-37, the receptor and its signal pathway and the function and its mechanism in RA, which provides references for the further study of IL-37 and RA.