Department of Otolaryngology, Head & Neck Surgery, the Second Hospital, Shanxi Medical University, Taiyuan, China.
Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Int Forum Allergy Rhinol. 2019 Jun;9(6):656-664. doi: 10.1002/alr.22301. Epub 2019 Feb 4.
The biased T helper 2 (Th2) responses play a critical role in the pathogenesis of allergy. The underlying mechanism is not fully understood yet. Survivin can regulate multiple cellular activities. This study aims to elucidate the role of survivin in the development and maintenance of Th2 polarization.
CD4 T cells were isolated from blood samples collected from patients with allergic asthma (AS) and HS control (HS) subjects. Mice carrying CD4 T cells with survivin knockout (KO mice) were employed to test the role of survivin in the development of the biased Th2 responses.
KO mice failed to induce airway allergy. Peripheral CD4 T cells expressed survivin, which was higher in the AS group than that in the HS group. Naive CD4 T cells with higher expression of survivin were prone to differentiating into Th2 cells. Survivin bound to the Il4 promoter in CD4 T cells to enhance Il4 gene transcription. The expression of Fas was lower in CD4 T cells of the AS group than that in the HS group. Overexpression of survivin suppressed the expression of Fas and impaired the activation-induced cell death (AICD) of CD4 T cells.
Survivin facilitates the development of biased Th2 polarization through promoting expression of interleukin 4 (IL-4) and impairing the AICD machinery of CD4 T cells. To modulate the expression of survivin in CD4 T cells has the translational potential in the treatment of allergic diseases.
偏置的辅助性 T 细胞 2（Th2）反应在过敏发病机制中起关键作用。但其潜在机制尚未完全阐明。Survivin 可调节多种细胞活动。本研究旨在阐明 Survivin 在 Th2 极化的发展和维持中的作用。
从过敏性哮喘（AS）患者和健康对照（HS）受试者的血液样本中分离 CD4 T 细胞。采用携带 Survivin 基因敲除（KO）的 CD4 T 细胞的小鼠来检测 Survivin 在偏向性 Th2 反应发展中的作用。
KO 小鼠未能诱导气道过敏。外周血 CD4 T 细胞表达 Survivin，AS 组高于 HS 组。高表达 Survivin 的初始 CD4 T 细胞更易分化为 Th2 细胞。Survivin 与 CD4 T 细胞中的 Il4 启动子结合，增强 Il4 基因转录。AS 组 CD4 T 细胞中 Fas 的表达低于 HS 组。Survivin 的过表达抑制 Fas 的表达，并损害 CD4 T 细胞的活化诱导细胞死亡（AICD）。
Survivin 通过促进白细胞介素 4（IL-4）的表达和损害 CD4 T 细胞的 AICD 机制，促进偏向性 Th2 极化的发展。调节 CD4 T 细胞中 Survivin 的表达具有治疗过敏性疾病的转化潜力。
