Jiang Yinan, Zhou Hongmin, Ma Dandan, Chen Zhonghua Klaus, Cai Xun
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Ministry of Health, and Key Laboratory of Ministry of Education, Wuhan, Hubei, China (mainland).
Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).
Med Sci Monit. 2015 May 28;21:1548-55. doi: 10.12659/MSM.894321.
MicroRNA-19a (miR-19a), an oncogenic microRNA, has been recently reported to target CD22 in B cell lymphoma cell lines, but its role in inflammatory response is unclear. CD22 is a negative regulator for BCR signaling, and we hypothesize that miR-19a regulates B cell response by targeting CD22 in sepsis.
In order to determine whether miR-19a-CD22 pathway was involved in sepsis, and what role it played in the regulatory mechanisms, we detected the levels of miR-19a in B cells obtained from patients with sepsis, and measured the levels of miR-19a and CD22 expression in B cells activated by LPS in vitro. Additionally, we investigated the correlation between miR-19a and CD22, as well as the influence of this pathway on BCR signaling, in transfected B cells.
We found that septic patients displayed up-regulated miR-19a in B cells. In vitro, miR-19a was increased in activated B cells, with CD22 expression initially enhanced but subsequently decreased. Moreover, overexpression of miR-19a resulted in an amplified BCR signaling, while overexpression of CD22 attenuated the effect of miR-19a and increased its expression.
Our study demonstrated that miR-19a and CD22 comprised a feedback loop for B cell response in sepsis, providing a potential therapeutic target to recover the immune homeostasis.
微小RNA-19a(miR-19a)是一种致癌性微小RNA,最近有报道称其在B细胞淋巴瘤细胞系中靶向CD22,但其在炎症反应中的作用尚不清楚。CD22是BCR信号传导的负调节因子,我们推测miR-19a在脓毒症中通过靶向CD22来调节B细胞反应。
为了确定miR-19a-CD22通路是否参与脓毒症及其在调节机制中所起的作用,我们检测了脓毒症患者B细胞中miR-19a的水平,并测定了体外经脂多糖(LPS)激活的B细胞中miR-19a和CD22的表达水平。此外,我们还研究了转染B细胞中miR-19a与CD22之间的相关性以及该通路对BCR信号传导的影响。
我们发现脓毒症患者的B细胞中miR-19a表达上调。在体外,激活的B细胞中miR-19a增加,CD22表达最初增强但随后降低。此外,miR-19a的过表达导致BCR信号传导增强,而CD22的过表达减弱了miR-19a的作用并增加了其表达。
我们的研究表明,miR-19a和CD22构成了脓毒症中B细胞反应的反馈回路,为恢复免疫稳态提供了潜在的治疗靶点。