Luo Xiang-Qian, Yang Shao-Bo, Qiu Shu-Qi, Xie Rui-Di, Yang Li-Tao, Ke Yu-Xing, Zhao Hong-Xia, Geng Xiao-Rui, Yang Gui, Liu Zhi-Qiang, Liu Jiang-Qi, Wang Shuai, Liu Da-Bo, Liu Jun
Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University Guangzhou 510010, China.
Department of Cadre Clinic, Chinese PLA General Hospital Beijing 100853, China.
Am J Transl Res. 2016 Dec 15;8(12):5766-5772. eCollection 2016.
The dysfunction of peripheral immune tolerance plays an important role in the pathogenesis of allergic diseases. Recent reports indicate that micro RNA (miR)-98 is associated with the process of aberrant immune responses. This study aims to test a hypothesis that miR-98 is associated with the pathogenesis of airway allergy via interfering with the development of regulatory B cells (Breg). In this study, patients with airway allergy were recruited into this study. The frequency of Bregs was assessed by flow cytometry. The levels of miR-98 in peripheral B cells were determined by RT-qPCR. A cell-culture model of B cells was developed to test the role of miR-98 in the repressing of interleukin (IL)-10 in B cells. The results showed that the levels of IL-10 in peripheral B cells were significantly lower in patients with airway allergy as compared with healthy subjects. High levels of miR-98 (one of the miR-98 members) were detected in peripheral B cells of patients with airway allergy, which was mimicked by stimulating B cells with IL-4. Histone acetyltransferase p300 was involved in the IL-4-induced miR-98 expression. miR-98 mediated the IL-4-inhibited IL-10 expression in B cells. In conclusion, miR-98 affects the expression of IL-10 in B cells and may be a novel therapeutic target for the treatment of allergic diseases.
外周免疫耐受功能障碍在过敏性疾病的发病机制中起重要作用。最近的报道表明,微小RNA(miR)-98与异常免疫反应过程有关。本研究旨在验证一个假设,即miR-98通过干扰调节性B细胞(Breg)的发育与气道过敏的发病机制相关。在本研究中,招募了气道过敏患者。通过流式细胞术评估Breg的频率。通过RT-qPCR测定外周B细胞中miR-98的水平。建立了B细胞的细胞培养模型,以测试miR-98在抑制B细胞中白细胞介素(IL)-10方面的作用。结果显示,与健康受试者相比,气道过敏患者外周B细胞中IL-10水平显著降低。在气道过敏患者的外周B细胞中检测到高水平的miR-98(miR-98成员之一),用IL-4刺激B细胞可模拟这一情况。组蛋白乙酰转移酶p300参与了IL-4诱导的miR-98表达。miR-98介导了IL-4抑制的B细胞中IL-10表达。总之,miR-98影响B细胞中IL-10的表达,可能是治疗过敏性疾病的一个新的治疗靶点。