白细胞介素22在类风湿关节炎中的作用机制研究

Mechanisms of interleukin-22 in rheumatoid arthritis

摘要

类风湿关节炎（RA）是一种以对称性小关节滑膜炎为病理特征的慢性自身免疫性疾病，其发病机制尚未完全阐明。近年研究发现白细胞介素（IL）-22在RA不同发病阶段及细胞因子微环境下的双重作用，主要表现为促炎、促骨破坏或在特定条件下发挥保护作用。本文系统回顾了IL-22在RA病程中的作用机制，归纳其激活下游信号网络影响成纤维样滑膜细胞与破骨细胞的新发现，分析其作为炎症和骨破坏关键调控因子的分子基础和临床转化潜力，为RA新型靶向治疗提供理论依据。IL-22是一种炎症细胞因子，通过与IL-22受体结合激活非受体型酪氨酸蛋白激酶（JAK）/信号转导及转录激活蛋白（STAT）、丝裂原活化蛋白激酶（MAPK）、核因子（NF）-κB和磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路，在细胞增殖、凋亡和免疫反应中发挥促炎和抗炎的双重作用，以调控成纤维样滑膜细胞和破骨细胞的生成、分化和免疫反应的方式参与RA的发生与发展，对RA患者的关节造成滑膜炎症、血管翳形成及骨质破坏。

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease pathologically characterized by symmetrical synovitis of small joints, and its pathogenesis has not yet been fully elucidated. Recent studies have found that interleukin-22 (IL-22) plays dual roles at different stages of RA and under different cytokine microenvironments, mainly exerting pro-inflammatory and bone destruction-promoting effects, or protective effects under specific conditions. This article systematically reviews the mechanisms of IL-22 in the course of RA, summarizes recent findings on its activation of downstream signaling networks affecting fibroblast-like synoviocytes (FLS) and osteoclasts (OC), and analyzes the molecular basis and clinical translational potential of IL-22 as a key regulator of inflammation and bone destruction, thereby providing a theoretical basis for novel targeted therapies for RA. IL-22 is an inflammatory cytokine that activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT), mitogen-activated protein kinase (MAPK), nuclear factor (NF)-κB, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathways by binding to the IL-22 receptor. It plays dual pro-inflammatory and anti-inflammatory roles in cell proliferation, apoptosis and immune responses. By regulating the generation, differentiation and immune responses of FLS and OC, IL-22 participates in the occurrence and development of RA, leading to synovial inflammation, pannus formation and bone destruction in the joints of patients with RA.

关键词

类风湿关节炎 / 白细胞介素 / IL-22 / 信号通路 / 破骨细胞

Key words

Rheumatoid arthritis / Interleukin / IL-22 / Signaling pathway / Osteoclast

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基金资助

国家自然科学基金(81960803)

广西壮族自治区自然科学基金项目(2023JJA140318)