PPARγ在自身免疫性疾病中的研究进展

Research progress of the role of PPARγ in autoimmune diseases

自身免疫性疾病(autoimmune diseases,AID)是由于自身免疫系统攻击自身组织产生的疾病。研究表明,自身免疫耐受的失衡及长期炎症反应无疑是AID发生的核心事件。过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)属于核激素受体超家族,是配体激活转录因子。PPARγ与维甲酸X受体(retinoid X receptor,RXR)结合形成异源二聚体;当PPAR被激活后,该复合体通过与位于每个基因调控位点的特定的过氧化物酶体增殖物反应元件(PPAR response element,PPRE)结合,进而发挥调控基因表达的作用。PPARγ具有多种生物学功能,在调节新陈代谢、控制炎症、调节糖脂代谢、改善动脉粥样硬化、抑制肿瘤和调节免疫过程中发挥重要作用。近几年研究表明,PPARγ参与多种AID的发病机制,其可能涉及调节巨噬细胞的激活和极化,调控树突状细胞功能,介导T细胞的增殖和分化及调节相关基质细胞的功能。本文就PPARγ的生物学功能、信号转导途径和激动剂对AID的保护作用及相关机制进行总结,旨在为相关疾病的机制研究和防治策略提供依据。

Autoimmune diseases(AID)are characterized by autoimmune disorder,as autologous tissue is attacked by the autoimmune system.It is reported that the imbalance of autoimmune tolerance and ingrained inflammatory response are the core events of AID undoubtedly.Peroxisome proliferator-activated receptorγ(PPARγ)which belongs to the nuclear hormone receptor superfamily is a ligand activated transcription factor.PPARγ combines with retinoid X receptor(RXR)to form heterodimer.When PPARγ is activated,the complex regulates gene expression by binding to a specific peroxisome proliferator response element(PPRE).In addition,PPARγ has diversified biological functions,playing important roles in regulating metabolism,controling inflammation,modulating glucose and lipid metabolism,ameliorating atherosclerosis,anti-tumor,and regulating immune response.However,recently researches indicate that PPARγ participates in the pathogenesis of AID.PPARγ plays key roles in regulating activation and polarization of macrophages,function of dendritic cells,proliferation and differentiation of T cells,and modulation of the function of related stromal cells.This article summarizes the biological functions and signal transduction pathways of PPARγ and the protective effects of agonists of PPARγ on AID,aiming to provide theoretical support for the research of mechanism and prevention and treatment of AID.