白细胞介素-10抑制类风湿关节炎患者的研究进展

Update on IL-10 Inhibition of Rheumatoid Arthritis

类风湿关节炎(RA)是以全身多处关节炎症为主的自身免疫性疾病。调节性B细胞(Breg)具有负向免疫调节作用,能调控炎症疾病发展和介导免疫耐受,目前认为具有表型CD19+CD27+CD24hiCD38hi的B细胞是分泌白细胞介素-10(IL-10)的Breg(B10细胞)的前体细胞。IL-10是重要的炎症抑制性细胞因子,可抑制IL-6、IL-12和IL-17等因子生成,并且能抑制Th细胞分化。有研究表明,RA患者疾病活动度与B10细胞表达成负相关,患者外周血中IL-10、TGF-β浓度水平也下降。骨髓间充质干细胞(BM-MSCs)已经被证实具有多向分化和自我更新能力,激活BM-MSCs的Wnt/β-catenin通路能挽救成骨细胞增殖抑制,减少脂肪细胞生成。目前广泛应用于实验动物模型炎症反应的治疗。此外,BM-MSCs被外界炎症因素刺激后能产生免疫调节因子,如IDO、PGE2、IL-10等。运用BM-MSCs调控免疫细胞分泌抑炎症介质IL-10,对控制自身免疫性疾病的发展,制定合理有效的针对RA等炎症免疫相关疾病治疗方案具有重要意义。

Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation of multiple joints throughout the body.Regulatory B cells(Breg)have negative immunomodulation effects,which can regulate the development of inflammatory diseases and mediate immunological tolerance.Currently,B cells with phenotypic CD27+CD19+CD24hiCD38hi are considered to be the precursor of Breg(B10)cells secreting IL-10.IL-10 is an important inflammatory inhibitory cytokine,which can inhibit the production of IL-6,IL-12,IL-17 and other factors,and inhibit the differentiation of Th cells.Studies have shown that the disease activity of RA patients is negatively correlated with the expression of B10 cells,and the concentration levels of IL-10 and TGF-βin the peripheral blood of patients also decrease.Bone marrow mesenchymal stem cells(BM-MSCs)have been shown to have multidirectional differentiation and self-renewal ability,and activation of the Wnt/β-catenin pathway in BM-MSCs can improve the proliferation inhibition of osteoblasts and reduce the generation of adipocytes.Currently,it is widely used in the treatment of inflammatory reactions in experimental animal models.In addition,BM-MSCs can produce immune regulators such as IDO,PGE2 and IL-10 after being stimulated by external inflammatory factors.The use of BM-MSCs to regulate the secretion of anti-inflammatory factor IL-10 by immune cells is of great significance for the control of the development of autoimmune diseases and the formulation of reasonable and effective treatment means for RA and other inflammatory immune-related diseases.