过敏性哮喘 z-bio 2025-01-09 433

　　Under the support of National Natural Science Foundation of China projects (approval numbers: 82025002, 82394411, 82170113), the team of Professor Zhang Huiyuan and Researcher Hu Hongbo from the Institute of Immunology and Hematology/National Key Laboratory of West China Hospital of Sichuan University, in collaboration with Professor Liu Xindong from Southwest Hospital of Army Medical University, has made progress in the research of allergic asthma. The research findings, titled "Hypoxia inducible factor 2 α promotes pathogenic polarization of stem like Th2 cells via modulation of phospholipid metabolism by regulating phospholipid metabolism," were published on December 10, 2024 in the journal Immunity. Paper link: https://www.cell.com/immunity/fulltext/ S1074-7613 (24) 00496-5.

　　Allergic asthma (abbreviated as asthma) is a common chronic respiratory immune disease, and its pathogenesis is mainly related to the abnormal activation of T helper 2 cells (Th2 cells) induced by allergens. Traditional treatment methods such as bronchodilators and glucocorticoids can effectively alleviate the symptoms of asthma patients, but cannot achieve a complete cure for asthma. In addition, for patients with severe asthma, drug resistance further limits the efficacy of existing treatment options. Therefore, exploring new treatment strategies, especially precise targeted therapy for pathogenic Th2 cells, has become a key research direction in the field of asthma treatment.

　　This study conducted single-cell analysis of CD4+T cells in patients with asthma and chronic sinusitis, and found that the expression of HIF2 α was significantly increased in pathogenic Th2 cells. Further experimental results showed that T cell specific knockout of HIF2 α significantly inhibited the differentiation of Th2 cells and alleviated asthma symptoms in mice. This study describes the heterogeneity of Th2 cells in asthma and reveals the core regulatory role of HIF2 α in the transformation of dry like Th2 cells into pathogenic Th2 cells (Figure). Based on the above findings, the study further evaluated the therapeutic potential of the HIF2 α - specific inhibitor PT-2385. The results showed that PT-2385 can significantly inhibit Th2 cell differentiation, effectively alleviate airway inflammation, and control asthma symptoms.

　　This study elucidates the key role of HIF2a in promoting phospholipid metabolism and regulating Th2 cell differentiation in the pathogenesis of allergic asthma, providing a new perspective for a deeper understanding of the immune pathogenesis of asthma and offering new ideas for precise targeting of HIF2 α in the treatment of allergic asthma.