Pathogenic conversion of regulatory B10 cells into osteoclast-priming cells in rheumatoid arthritis
Pathogenic conversion of regulatory B10 cells into osteoclast-priming cells in rheumatoid arthritis
复制标题
类风湿性关节炎中调节性 B10 细胞向破骨细胞启动细胞的致病性转化
DOI：
10.1016/j.jaut.2016.09.002
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发表时间：
2017-01-01
影响因子：
12.8
通讯作者：
Jia, Yuan
中科院分区：
文献类型：
--
作者：
Hu, Fanlei;Liu, Hongjiang;Jia, Yuan
类风湿关节炎（RA）的调节性B10细胞功能受损，但机制尚不清楚。B细胞通过产生RANKL被认为是破骨细胞形成的重要参与者。在本研究中，我们研究了调节性B10细胞是否可以转化为产生rankl的细胞，从而损害其在RA中的免疫抑制功能并加剧疾病进展。结果表明，人B10调节性细胞可以异位表达RANKL。在RA环境下，产生rankl的B10细胞在TNF-a的部分诱导下急剧扩增。这些细胞的频率与RA患者疾病活动和压痛关节计数呈正相关，而与调节性B10细胞的频率负相关。引人注目的是，来自RA患者而非健康个体的产生ranklb10细胞以旁分泌和细胞-细胞接触依赖的方式显著促进破骨细胞分化和骨侵蚀。此外，在治疗后疾病缓解的RA患者中，这些致病性产生rankl的B10细胞减少，而产生il -10的调节性B10细胞增加。总之，这些结果表明，在RA中，调节性B10细胞表现出转化为产生rankl的细胞的潜力，从而加剧破骨细胞的形成、骨破坏和疾病进展。调节B10细胞的状态可能为RA的治疗提供新的策略。(C) 2016 Elsevier Ltd.版权所有。
Regulatory B10 cells were functionally impaired in rheumatoid arthritis (RA), yet the mechanisms were unclear. B cells are recently recognized as important participants in osteoclastogenesis by producing RANKL. In this study, we investigated whether regulatory B10 cells could convert into RANKL-producing cells, thus impairing their immunosuppressive functions in RA and exacerbating the disease progression. Our results showed that human regulatory B10 cells could ectopically express RANKL. Under RA circumstance, RANKL-producing B10 cells expanded dramatically, partially induced by TNF-a. The frequencies of these cells were positively correlated with RA patient disease activities and tender joint counts, but negatively correlated with the frequencies of regulatory B10 cells. Strikingly, RANKLproducing B10 cells from RA patients, but not healthy individuals significantly promoted osteoclast differentiation and bone erosion in a paracrine and cell-cell contact-dependent manner. Moreover, these pathogenic RANKL-producing B10 cells declined while regulatory IL-10-producing B10 cells increased in RA patients with disease remission after therapy. Collectively, these results showed that in RA, regulatory B10 cells demonstrated the potential of converting into RANKL-producing cells, thus exacerbating osteoclast formation, bone destruction and disease progression. Modulating the status of B10 cells might provide novel therapeutic strategies for RA. (C) 2016 Elsevier Ltd. All rights reserved.