针刺通过下调IL-33/ST2通路抑制哮喘2型固有淋巴细胞功能的机制研究

Under the stimulus of epithelium-derived cytokines IL-25 and IL-33, type 2 innate lymphoid cell (ILC2) can secrete a large number of Th2 cytokines such as IL-5 and IL-13 which will promote the occurrence of asthma through participating in the type II immune response. Although the clinical and experimental studies have proved the effectiveness of acupuncture in treating asthma by regulating the inflammatory function of T cell, it is still unclear that if acupuncture has effect on ILC2. Our previous studies have found that acupuncture can reduce the content of IL-33 from peripheral blood during the treatment of asthma. While the expression of IL-33 receptor ST2 on the surface of ILC2 is an important guarantee for its secretion of cytokines. These results suggest that acupuncture may reduce the IL-33 levels to regulat the secretion of Th2 type cytokines by ILC2. Recent studies have also found that acupuncture can alleviate formalin-induced inflammatory pain by the inhibition of spinal IL-33/ST2 signaling pathway. Based on the above research results, we proposed the hypothesis that acupuncture can inhibit the immune function of ILC2 by the inhibition IL-33/ST2 pathway in asthma. In this project, we intend to study the effect of acupuncture on ILC2 function and verify the IL-33/ST2 pathway in lung tissue of asthmatic mice, in order to provide a new method for the treatment of asthma.

2型固有淋巴细胞(ILC2)在IL-25、IL-33等细胞因子的刺激下可以分泌IL-5和IL-13，参与II型免疫反应，促进哮喘的发生。虽然临床及实验研究证明针刺治疗哮喘有效，并可以调节T细胞免疫，但针刺对ILC-2是否有作用仍不清楚。我们前期研究发现，针刺在治疗哮喘的同时能减少外周血IL-33含量，而ILC2表面表达IL-33的受体ST2是其分泌细胞因子的重要保证，这提示针刺抗哮喘可能通过降低IL-33水平而影响ILC2对Th2型细胞因子的分泌。最近研究还发现针刺可以通过下调脊髓神经元的IL-33/ST2通路抑制福尔马林诱导的小鼠炎性疼痛。根据上述研究结果，我们提出了针刺通过下调IL-33/ST2通路抑制ILC2免疫功能抗哮喘的假说。本项目中，我们拟研究针刺对哮喘模型小鼠肺组织ILC2功能的影响及对IL-33/ST2通路的调控及验证来探讨针刺抗哮喘的作用及机制，为哮喘治疗提供新的思路。

2型固有淋巴细胞(ILC2)在IL-25、IL-33等细胞因子的刺激下可以分泌IL-5和IL-13，参与II型免疫反应，促进哮喘的发生。虽然临床及实验研究证明针刺治疗哮喘有效，并可以调节T细胞免疫，但针刺对ILC-2是否有作用仍不清楚。我们通过实验研究发现，给予针刺治疗后，哮喘小鼠呼吸功能、肺组织病理表现以及肺泡灌洗液炎症细胞数量和IL-5、IL-13、IL-9、sST2、IL-33、IL-25等炎症因子表达量均有所改善，说明针刺具有抗哮喘治疗作用；针刺在治疗哮喘的同时能减少肺组织ILC2和外周血IL-33含量，而ILC2表面表达IL-33的受体ST2是其分泌细胞因子的重要保证，这提示针刺抗哮喘可能通过IL-33/ST2通路对肺ILC2募集具有抑制作用。流式分选并体外培养ILC2发现针刺血清可调低ILC2的IL-5表达情况，说明针刺可对ILC2细胞功能进行调控；敲除IL-33/ST2通路重要组分ST2后发现，KO组造模成功，但KO组的气道阻力明显优于WT组，说明哮喘的特征可能部分通过IL-33/ST2通路完成。结合前期的动物实验及细胞实验，IL-33/ST2是调控哮喘ILC2功能的重要信号通路，针刺可通过下调IL-33/ST2通路抑制ILC2在肺组织中的募集，从而起到抗哮喘作用。