首都医科大学学报 ›› 2017, Vol. 38 ›› Issue (5): 640-644.doi: 10.3969/j.issn.1006-7795.2017.05.002

• 皮肤病性病诊疗与研究 • 上一篇    下一篇

B细胞活化因子的双向性:促进调节性T细胞分泌白细胞介素-35

张亚敏, 王瑞云, 李军, 陶娟, 涂亚庭   

  1. 华中科技大学同济医学院附属协和医院皮肤科, 武汉 430022
  • 收稿日期:2017-05-09 出版日期:2017-09-21 发布日期:2017-10-18
  • 通讯作者: 涂亚庭 E-mail:yatingtu@yahoo.com.cn
  • 基金资助:
    国家自然科学基金(81573047,81602760)。

Dichotomous effect of BAFF:inducing IL-35 production by regulatory T cells

Zhang Yamin, Wang Ruiyun, Li Jun, Tao Juan, Tu Yating   

  1. Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology(HUST), Wuhan 430022, China
  • Received:2017-05-09 Online:2017-09-21 Published:2017-10-18
  • Supported by:
    This study was supported by National Natural Science Foundation of China (81573047, 81602760).

摘要: 目的 研究B细胞活化因子(B cell activation factor of the tumor necrosis factor family,BAFF)对调节性T细胞(Tregs)分泌抑制性细胞因子白细胞介素-35(interleukin-35,IL-35)的影响,验证系统性红斑狼疮(systemic lupus erythematosus,SLE)中BAFF对免疫反应的双向调节机制。方法 磁珠分选狼疮模型鼠Tregs,经BAFF刺激后采用qRT-PCR及流式细胞术检测其分泌IL-35浓度。比较正常对照鼠、狼疮模型鼠及经尾静脉注射抗BAFF蛋白后狼疮模型鼠脾脏Tregs频率及分泌IL-35情况。结果 BAFF能够有效促进Tregs分泌IL-35。相对于正常对照鼠,狼疮模型鼠(血清中BAFF升高)脾脏Tregs分泌较高浓度的IL-35,而中和其循环中BAFF后,Tregs分泌IL-35减少。结论 在SLE发病机制中,BAFF不仅是重要的致病因素,还能够通过促进Tregs细胞分泌IL-35发挥负向免疫调节效应。

关键词: 系统性红斑狼疮, B细胞活化因子, 调节性T细胞, 白细胞介素-35

Abstract: Objective The purpose of this study was to determine whether B cell activation factor of the tumor necrosis factor (TNF) family (BAFF) has an effect on the production of interleukin-35 (IL-35) by regulatory T cells (Tregs), further identifying the dichotomous regulator of BAFF on immune responses in systemic lupus erythematosus (SLE). Methods Splenic CD4+ CD25+ T cells were sorted by magnetic isolation and stimulated with BAFF. The production of IL-35 was determined by flow cytometry and quantitative RT-PCR. Furthermore, the frequency of IL-35 producing Tregs in spleen from wild-type (WT) controls, MRL-Faslpr/lpr mice and anti-BAFF protein treated MRL-Faslpr/lpr mice was also analyzed by flow cytometry. Results We found that BAFF could promote Tregs to produce IL-35 in vitro. Flow cytometric analysis showed that the frequency of IL-35 producing Tregs was much higher in spleen of MRL-Faslpr/lpr mice which have increased serum level of BAFF compared with those in WT controls. Whereas anti-BAFF treatment weakened this effect. Conclusion In the pathogenesis of SLE, BAFF is not only a key pathogenic factor but also has immunosuppressive effect by promoting Tregs to produce IL-35.

Key words: systemic lupus erythematosus (SLE), B cell activation factor of the tumor necrosis factor family (BAFF), regulatory T cells, interleukin-35 (IL-35)

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