哮喘（Asthma）是一种由多种复杂因素引起的呼吸道慢性炎症疾病，具有可逆性气道阻塞、气道高反应性和气道炎症等特征。我国哮喘患者超过 3000 万，且在儿童和成年人中都有较高的发病几率，这使哮喘成为了最为常见的慢性病之一。本课题创新地提出，来自肺部菌群的维生素B6有可能作为SHMT2的辅酶，通过调控 IL-33 的泛素化降解，进而影响二型先天性淋巴细胞(ILC2)介导的呼吸道炎症反应。通过体内及体外实验，我们将重点探究IL-33泛素化降解的分子生物学机制，使我们更加了解IL-33的生理学及病理学功能；与此同时，研究维生素B6是否是肺部菌群影响哮喘的中间媒介，有利于开发更有针对性的哮喘疗法，实现个性化治疗。本课题的深入探究将为哮喘的病因和致病机制提供理论依据，为临床治疗提供新思路。

Asthma is a chronic inflammatory disease of the respiratory tract caused by a variety of complex factors, characterized by reversible airway obstruction, airway hyperresponsiveness, and airway inflammation. Asthma is one of the most common chronic diseases in China, with more than 30 million patients and a high incidence among children and adults. Our project innovatively puts forward a hypothesis that vitamin B6 from the pulmonary flora may act as a coenzyme of SHMT2 to regulate the degradation of IL-33 through ubiquitination, which in turn affects the respiratory inflammatory response mediated by type 2 innate lymphoid cells (ILC2s). Through in vivo and in vitro experiments, we will focus on exploring the molecular biological mechanisms ubiquitination-mediated IL-33 degradation, so that we can better understand the physiological and pathological functions of IL-33. At the same time, to study whether vitamin B6 is an intermediate medium for lung flora to affect asthma is conducive to the development of more targeted asthma therapy and personalized treatment. The further investigation of this subject will provide a theoretical basis for the etiology and pathogenic mechanism of asthma and provide new ideas for clinical treatment.