Jin-Mei Xue1, Mei-Zhen Zhao2,3, Fei Ma4, Shan-Shan Li2, Li-Hua Mo5, Xian-Hai Zeng2,3, Yong-Jin Wu2,3, Jiang-Qi Liu2,3, Tian-Yong Hu2,3, Rui-Di Xie2, Zhi-Gang Liu2, Chang-Qing Zhao1, Ping-Chang Yang2. 1. Department of Otolaryngology, Head & Neck Surgery, the Second Hospital, Shanxi Medical University, Taiyuan, China. 2. Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China. 3. Shenzhen ENT Institute & Longgang ENT Hospital, Shenzhen, China. 4. Department of Otolaryngology, Head & Neck Surgery, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. 5. Department of Pediatric Otolaryngology, Southern Medical University Shenzhen Hospital, Shenzhen, China.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. METHODS: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. RESULTS: 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. CONCLUSION: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.