Immunoregulatory role of IL-35 in T cells of patients with rheumatoid arthritis
Immunoregulatory role of IL-35 in T cells of patients with rheumatoid arthritis
复制标题
DOI：
10.1093/rheumatology/keu528
复制
发表时间：
2015-08-01
期刊：
影响因子：
5.5
通讯作者：
Takasaki, Yoshinari
中科院分区：
文献类型：
--
作者：
Nakano, Souichiro;Morimoto, Shinji;Takasaki, Yoshinari
Objective. IL-35是IL-12家族中最新发现的成员。它由EBV诱导基因3（EBI 3）和IL-12 α链p35组成。我们研究了IL-35是否能增强RA患者外周血的体外免疫抑制功能。从17名活动期和10名非活动期RA患者收集外周血，并使用ELISA定量IL-35浓度。通过共价连接EBI 3和IL-12 α（p35）构建含有在羧基末端具有FLAG标签的IL-35的表达载体。然后使用从人RA患者分离的T细胞与CD 2、CD 3和CD 28抗体在抑制测定中评估IL-35的功能。活动期RA患者血清IL-35水平和Treg数量明显降低。活动期RA患者血清IL-35水平与28关节DAS和ESR（DAS 28-ESR）呈显著相关。IL-35处理增强了调节功能，抑制了IL-17和IFN-γ等炎性细胞因子的水平以及与CD 2、CD 3和CD 28结合刺激的效应T细胞的细胞生长。提示IL-35可抑制RA外周免疫应答过程中T细胞的活化。因此，我们的数据表明IL-35可能具有多个治疗靶点。
Objective. IL-35 is the most recently identified member of the IL-12 family. It consists of EBV-induced gene 3 (EBI3) and IL-12 alpha chain p35. We investigated whether IL-35 enhances the in vitro immunosuppressive function of peripheral blood isolated from patients with RA.Methods. Peripheral blood was harvested from 17 active and 10 inactive RA patients and IL-35 concentrations were quantified using an ELISA. An expression vector containing IL-35 with a FLAG tag at the carboxyl-terminus was constructed by covalently linking EBI3 and IL-12 alpha (p35). The function of IL-35 was then evaluated in a suppression assay using T cells isolated from human RA patients with CD2, CD3 and CD28 antibodies.Results. Serum IL-35 levels and the number of Treg were decreased significantly in patients with active RA. There was a significant correlation between serum IL-35 and the 28-joint DAS with ESR (DAS28-ESR) in patients with active RA. IL-35 treatment enhanced the regulatory function, suppressing the levels of inflammatory cytokines such as IL-17 and IFN-gamma and the cellular growth of effector T cells stimulated by conjugation with CD2, CD3 and CD28.Conclusion. These data revealed that IL-35 might suppress T cell activation during the peripheral immune responses of RA. Therefore our data suggest that IL-35 might have multiple therapeutic targets.