IL-35/iTr35细胞调控哮喘炎症亚型的分子机制研究

过敏原特异性Th1/Th2/Th17细胞功能异常在哮喘发病机制中起重要作用，抑制其病理活性是研究前沿。新近发现的IL-35/iTr35细胞调节Th1/Th2/Th17生物活性，从而调节免疫炎症，但是否能调节哮喘病理性Th细胞功能，影响哮喘炎症亚型的病理过程和具体机制尚不清楚。我们前期工作证明IL-35在四种不同哮喘炎症亚型中表达不同，与炎症细胞及细胞因子水平呈显著相关。推测：IL-35通过促进Th1细胞、抑制Th2、Th17细胞分化及活性，从而调节过敏性哮喘气道炎症。我们拟在人体、动物和细胞水平，利用基因敲除小鼠、Microarray和磷酸多肽质谱指纹分析等方法，研究验证IL-35/iTr35细胞在不同哮喘炎症亚型中的功能作用、与Th1、Th2、Th17细胞数量的关系；揭示其调节上述细胞分化及活性的分子机制；阐明其在哮喘气道炎症发生发展中的作用机制，为临床治疗哮喘提供新靶点和依据。

Allergen-specific Th1 / Th2 / Th17 cell dysfunction plays an important role in the pathogenesis of asthma, and inhibiting its pathological activity is the frontier of research. The newly discovered IL-35 / iTr35 cells regulate Th1 / Th2 / Th17 biological activity, thereby suppressing inflammation. However, whether this cell can regulate the pathological Th cell function of asthma, affecting the pathological process and specific mechanism of asthma inflammation subtypes is not clear. Our previous work has shown that IL-35 is expressed differently in four different subtypes of asthma inflammation, which is significantly related to the levels of inflammatory cells and cytokines. It is speculated that IL-35 regulates the airway inflammation of allergic asthma by promoting Th1 cells and inhibiting Th2 and Th17 cell differentiation and activity. We plan to use gene knockout mice, Microarray and phosphopeptide mass spectrometry fingerprint analysis at human, animal and cell levels to study the functional role of IL-35 / iTr35 cells in different asthma inflammation subtypes, and its relationship with Th1 , Th2 and Th17 cell counts; to reveal its molecular mechanism regulating the above-mentioned cell differentiation and activity; to elucidate its mechanism of action in the development of asthma airway inflammation, providing new targets and basis for clinical treatment of asthma.