结节病的发病机制与临床治疗研究进展

Progress in pathogenesis and clinical treatment of sarcoidosis

结节病可累及全身多个重要脏器,导致器官功能不可逆损害,其发病机制至今仍未明确。目前的研究认为结节病是一个多因素导致的疾病,易感基因可能构成遗传本底,病原体感染、自身抗原不耐受、无机物接触等因素可诱发疾病的发生。这些致病抗原暴露后,模式识别受体、抗原呈递、吞噬与自噬等免疫和炎症相关通路的异常导致巨噬细胞功能改变,CD4~+T细胞过度激活,Th1和Th17亚群分泌大量白介素(interleukin,IL)-12、干扰素γ、肿瘤坏死因子α、IL-17和IL-23等细胞因子,诱导巨噬细胞聚集融合并形成肉芽肿,产生持续炎症。文章主要对结节病的发病机制相关研究作一综合阐述,并总结目前的临床治疗进展。

Sarcoidosis is a systemic disease which could affect many crucial organs and eventually cause irreversible functional damage to these organs.However,the pathogenesis of sarcoidosis is still not clear.Current studies suggest that sarcoidosis is caused by multiple factors.Individuals with certain genetic variations are highly susceptible to certain types of sarcoidosis.Furthermore,exposure to extrinsic antigenic factors such as pathogens or inorganic factors and intolerance of self-antigens also play a crucial role in the pathogenesis of sarcoidosis.Subsequent to antigenic stimulation,abnormality in pathways of pattern recognition receptor,phagosome or autophagy stimulates the activity of CD4+T cells which release inflammatory cytokines such as interleukin(IL)-12,interferon-γ,tumor necrosis factor-α,IL-17,and IL-23,thus fostering the proliferation of Th1 and Th17 subpopulation and inducing the fusion of macrophages to form granulomas.Here we aim to review mechanistic studies in the past decade and list current therapeutic methods to provide some insights into the etiology,pathogenesis and management of sarcoidosis.