Qu Shuo-Yao, He Ya-Long, Zhang Jian, Wu Chang-Gui
Department of Pulmonary and Critical Care Medicine, Fourth Military Medical University, Xi'an, China.
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Immunology. 2017 Sep;152(1):115-124. doi: 10.1111/imm.12753. Epub 2017 Jul 19.
Basophils (BA) play an important role in the promotion of aberrant T helper type 2 (Th2) immune responses in asthma. It is not only the effective cell, but also modulates the initiation of Th2 immune responses. We earlier demonstrated that Notch signalling regulates the biological function of BAin vitro. However, whether this pathway plays the same role in vivo is not clear. The purpose of the present study was to investigate the effect of Notch signalling on BA function in the regulation of allergic airway inflammation in a murine model of asthma. Bone marrow BA were prepared by bone marrow cell culture in the presence of recombinant interleukin-3 (rIL-3; 300 pg/ml) for 7 days, followed by isolation of the CD49b microbeads. The recombination signal binding protein J (RBP-J ) BA were co-cultured with T cells, and the supernatant and the T-cell subtypes were examined. The results indicated disruption of the capacity of BA for antigen presentation alongside an up-regulation of the immunoregulatory function. This was possibly due to the low expression of OX40L in the RBP-J BA. Basophils were adoptively transferred to ovalbumin-sensitized recipient mice, to establish an asthma model. Lung pathology, cytokine profiles of brobchoalveolar fluid, airway hyperactivity and the absolute number of Th1/Th2 cells in lungs were determined. Overall, our results indicate that the RBP-J-mediated Notch signalling is critical for BA-dependent immunoregulation. Deficiency of RBP-J influences the immunoregulatory functions of BA, which include activation of T cells and their differentiation into T helper cell subtypes. The Notch signalling pathway is a potential therapeutic target for BA-based immunotherapy against asthma.
嗜碱性粒细胞（BA）在促进哮喘中异常的2型辅助性T细胞（Th2）免疫反应方面发挥着重要作用。它不仅是效应细胞，还能调节Th2免疫反应的启动。我们之前证明Notch信号通路在体外调节BA的生物学功能。然而，该通路在体内是否发挥相同作用尚不清楚。本研究的目的是在哮喘小鼠模型中研究Notch信号通路对BA功能在调节过敏性气道炎症中的作用。通过在重组白细胞介素-3（rIL-3；300 pg/ml）存在下进行骨髓细胞培养7天来制备骨髓BA，随后分离CD49b微珠。将重组信号结合蛋白J（RBP-J）BA与T细胞共培养，并检测上清液和T细胞亚型。结果表明BA的抗原呈递能力受到破坏，同时免疫调节功能上调。这可能是由于RBP-J BA中OX40L表达较低所致。将嗜碱性粒细胞过继转移到卵清蛋白致敏的受体小鼠中，以建立哮喘模型。测定肺部病理学、支气管肺泡灌洗液的细胞因子谱、气道高反应性以及肺中Th1/Th2细胞的绝对数量。总体而言，我们的结果表明RBP-J介导的Notch信号通路对于BA依赖性免疫调节至关重要。RBP-J的缺乏影响BA的免疫调节功能，包括T细胞的激活及其分化为辅助性T细胞亚型。Notch信号通路是基于BA的哮喘免疫治疗的潜在治疗靶点。
