Lin Ri-Tian, Liu Jiang-Qi, Lu Hui-Ying, Chen Ya-Mei, Guan Li, Liu Zhi-Gang, Liu Zhan-Ju, Yang Ping-Chang
Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China.
The Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen 518060, China.
Oncotarget. 2017 Jun 28;8(40):67497-67505. doi: 10.18632/oncotarget.18723. eCollection 2017 Sep 15.
The pathogenesis of food allergy (FA) is to be further investigated. Regulatory B cells (B10 cell) play a critical in the maintenance of the homeostasis in the intestine. Deregulation of B10 cell is associated with immune inflammation. Micro RNA (miR) 155 is involved in affecting immune cell function. This study tests a hypothesis that miR-155 affects the B10 cell function to facilitate the initiation of FA. In this study, BALB/c mice were sensitized to ovalbumin (OVA) to induce FA-like inflammation in the intestine. B cells were isolated from the intestine by magnetic cell sorting. The expression of miR-155 and IL-10 in B cells was assessed by real time RT-PCR. The results showed that mice sensitized to OVA showed FA-like inflammation and lower frequency of B10 cell in the intestine. B cells isolated from the intestine of FA mice showed higher levels of miR-155 and lower levels of IL-10. Although all the three T helper (Th)2 cytokines, including interleukin (IL)-4, IL-5 and IL-13, were higher in the serum, only IL-13 was positively correlated with the levels of miR-155 in the intestinal B cells. Exposure to IL-13 in the culture markedly increased the expression of miR-155 and suppressed the expression of IL-10 in B cells. Blocking miR-155 abolished the IL-13-induced IL-10 suppression in B cells and inhibited FA response in mice. In conclusion, miR-155 plays a critical role in the initiation of FA in mice. Blocking miR-155 has therapeutic potential in the treatment of FA.
食物过敏（FA）的发病机制有待进一步研究。调节性B细胞（B10细胞）在维持肠道内环境稳定中起关键作用。B10细胞失调与免疫炎症相关。微小RNA（miR）155参与影响免疫细胞功能。本研究检验了一个假说，即miR - 155影响B10细胞功能以促进食物过敏的发生。在本研究中，用卵清蛋白（OVA）致敏BALB/c小鼠以诱导肠道内类似食物过敏的炎症。通过磁珠细胞分选从肠道分离B细胞。采用实时逆转录聚合酶链反应评估B细胞中miR - 155和白细胞介素10（IL - 10）的表达。结果显示，对OVA致敏的小鼠表现出类似食物过敏的炎症，且肠道中B10细胞频率降低。从食物过敏小鼠肠道分离的B细胞显示出较高水平的miR - 155和较低水平的IL - 10。尽管血清中所有三种辅助性T细胞（Th）2细胞因子，包括白细胞介素（IL）-4、IL - 5和IL - 13都较高，但只有IL - 13与肠道B细胞中miR - 155的水平呈正相关。在培养中暴露于IL - 13显著增加了B细胞中miR - 155的表达并抑制了IL - 10的表达。阻断miR - 155消除了IL - 13诱导的B细胞中IL - 10的抑制，并抑制了小鼠的食物过敏反应。总之，miR - 155在小鼠食物过敏的发生中起关键作用。阻断miR - 155在食物过敏治疗中具有治疗潜力。
