NLRP3细胞焦亡调控ILC2s-NMU1轴在气道高反应中的作用机制及针刺干预机制

气道高反应（AHR）患者易在医疗干预等刺激下发生气道水肿、痉挛，影响生活质量，威胁生命安全。本课题组既往通过ATG5-/-小鼠证实针刺通过ATG5调控AHR自噬及T淋巴细胞亚群稳态减轻哮喘小鼠症状。最新研究发现焦亡关键因子NLRP3引起IL-1β增加，激活AHR及免疫应答；针刺抑制NLRP3激活减少IL-1β，减轻肺部损伤，且2型先天型淋巴细胞（ILC2s）参与的神经-免疫轴起重要作用。但针刺干预AHR免疫调节的机制尚不明晰。因此，我们推测针刺通过NLRP3调节焦亡产物IL-1β分泌，激活ILC2s参与神经免疫调控T淋巴细胞亚群分化和功能治疗哮喘AHR症状。本课题拟采用NLRP3-/-小鼠探讨针刺对焦亡及ILC2s的调控机制；再采用人支气管上皮细胞系(HBE4)和原代ILC2s探讨NLRP3介导的焦亡引起的ILCs相关免疫环境改变和针刺的作用。为探讨针刺治疗哮喘AHR机制提供新的理论依据。

Patients with airway hyperresponsiveness (AHR) are prone to airway edema and spasm under stimulation of medical intervention, which severely affecting the living quality and even threatening safety of life. Our group have confirmed that acupuncture can regulate autophagy and T lymphocyte subgroup homeostasis through the ATG5 gene to relieve AHR symptoms in asthma by using ATG5flox/flox mice. Recent study found that NLRP3, a key factor of pyroptosis, can increase IL-1β, activate AHR and immune response.An other study found that acupuncture can inhibit the release of IL-1β by inhibiting the activation of NLRP3 and reduce acute lung injury, meanwhile, the neuro-immune axis involved type 2 innate lymphocytes (ILC2s) plays an important role in this process. However, the mechanism of acupuncture intervention in regulation of AHR immune is still unclear.Therefore, we speculate that acupuncture could regulate the secretion of pyroptosis product IL-1β through NLRP3, and activates ILC2s to participate in neuroimmune regulation of T lymphocyte subset differentiation and function to treat AHR in asthma. We intend to use transgenic C57BL mice(NLRP3-/-) to investigate the mechanism of acupuncture on immune regulation with ILC2s and pyroptosis; and then use human bronchial epithelial cell line (HBE4) and primary splenic ILC2s to investigate the changes of ILCs-related immune environment caused by NLRP3-mediated pyroptosis, and role of acupuncture in it. It could provide a new theoretical basis for exploring the mechanism of acupuncture in treating airway hyperresponsiveness in asthma.