Department of Pediatric Otolaryngology, Shenzhen Hospital, and The Third School of Clinical Medicine, Southern Medical University, Shenzhen, China.
Department of Otolaryngology, Longgang Central Hospital, Guangdong University of Chinese Traditional Medicine Shenzhen Clinical College, Room A7-509 at Lihu Campus, Shenzhen, 518055, China.
Cell Commun Signal. 2024 Sep 30;22(1):462. doi: 10.1186/s12964-024-01824-2.
Improvement is needed in the remedies used to control Th2 polarization. Bioengineering approaches have modified immune cells that have immunosuppressive functions. This study aims to generate modified eosinophils (Meos) in vivo and use Meos to balance Th2 polarization and reduce airway allergy.
A cell editor was constructed. The editor contained a peptide carrier, an anti-siglec F antibody, MHC II, ovalbumin, and LgDNA (DNA extracted from a probiotic, Lactobacillus rhamnosus GG). Which was designated as Cedit. Meos are eosinophils modified using Cedits. An airway Th2 polarization mouse model was established used to test the effect of Meos on suppressing airway allergy.
The Cedits remained physically and chemically stable in solution (pH7.2) for at least 96 h. Cedits specifically bound to eosinophils, which are designated as Meos. Meos produced programmed death ligand-1 (PD-L1); the latter induced antigen specific CD4 T cell apoptosis. Administration of Cedits through nasal instillations generated Meos in vivo, which significantly reduced the frequency of antigen specific CD4 T cells in the airways, and mitigated airway Th2 polarization.
We constructed Cedit, which could edit eosinophils into Meos in vivo. Meos could induce antigen specific CD4 T cell apoptosis, and reconcile airway Th2 polarization.
需要改进用于控制 Th2 极化的疗法。生物工程方法已经修饰了具有免疫抑制功能的免疫细胞。本研究旨在体内生成修饰的嗜酸性粒细胞(Meos),并利用 Meos 来平衡 Th2 极化和减少气道过敏。
构建了一种细胞编辑器。该编辑器包含肽载体、抗 Siglec F 抗体、MHC II、卵清蛋白和 LgDNA(从益生菌鼠李糖乳杆菌 GG 中提取的 DNA)。将其命名为 Cedit。使用 Cedits 修饰嗜酸性粒细胞,得到 Meos。建立气道 Th2 极化小鼠模型,以测试 Meos 对抑制气道过敏的作用。
Cedits 在溶液(pH7.2)中至少稳定 96 小时,理化性质稳定。Cedits 特异性结合嗜酸性粒细胞,被标记为 Meos。Meos 产生程序性死亡配体 1(PD-L1),后者诱导抗原特异性 CD4 T 细胞凋亡。通过鼻腔滴注给予 Cedits 可在体内生成 Meos,显著降低气道中抗原特异性 CD4 T 细胞的频率,并减轻气道 Th2 极化。
我们构建了 Cedit,可将嗜酸性粒细胞在体内编辑为 Meos。Meos 可诱导抗原特异性 CD4 T 细胞凋亡,并调节气道 Th2 极化。