Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
J Leukoc Biol. 2019 Apr;105(4):719-727. doi: 10.1002/JLB.3A0718-287RR. Epub 2019 Jan 29.
T helper (Th)2 polarization plays an important role in the pathogenesis of allergic diseases; the underlying mechanism remains to be further investigated. B cell lymphoma protein-2 like protein-12 (Bcl2L12) has the anti-apoptotic function. This study aims to elucidate the contribution of Bcl2L12 to Th2 polarization in patients with allergic rhinitis (AR). In this study, human CD4 T cells were isolated from blood samples collected from AR patients and healthy control (HC) subjects. The immune response profiles of CD4 T cells were analyzed by immunologic approaches. The results showed that AR CD4 T cells (CD4 T cells collected from AR patients) showed defects of apoptosis. The expression of FasL in AR CD4 T cells was lower than that of HC CD4 T cells. Serum IL-5 levels were negatively correlated with the expression of FasL in AR CD4 T cells. Exposure of CD4 T cells to IL-5 in the culture suppressed the expression of FasL and increased the expression of Bcl2L12. IL-5 increased the levels of Bcl2L12 in CD4 T cells, the latter bound to the FasL promoter to prevent FasL gene transcription. Inhibition of Bcl2L12 restored the apoptosis machinery in AR CD4 T cells. In conclusion, overexpression of Bcl2L12 in CD4 T cells compromises the apoptosis machinery; the latter can be restored by inhibition of Bcl2L12. BcL2L12 in CD4 T cells may be a novel target for the treatment of AR and other allergic disorders.
辅助性 T 细胞（Th）2 极化在过敏疾病的发病机制中起着重要作用；其潜在机制仍需进一步研究。B 细胞淋巴瘤蛋白-2 样蛋白-12（Bcl2L12）具有抗凋亡作用。本研究旨在阐明 Bcl2L12 对过敏性鼻炎（AR）患者 Th2 极化的贡献。在这项研究中，从 AR 患者和健康对照（HC）受试者采集的血液样本中分离出人 CD4 T 细胞。通过免疫方法分析 CD4 T 细胞的免疫反应谱。结果表明，AR CD4 T 细胞（从 AR 患者中采集的 CD4 T 细胞）表现出凋亡缺陷。AR CD4 T 细胞中 FasL 的表达低于 HC CD4 T 细胞。AR CD4 T 细胞中 FasL 的表达与血清 IL-5 水平呈负相关。在培养物中暴露于 IL-5 会抑制 CD4 T 细胞中 FasL 的表达并增加 Bcl2L12 的表达。IL-5 增加了 CD4 T 细胞中 Bcl2L12 的水平，后者与 FasL 启动子结合以防止 FasL 基因转录。抑制 Bcl2L12 可恢复 AR CD4 T 细胞中的凋亡机制。总之，Bcl2L12 在 CD4 T 细胞中的过表达会损害凋亡机制；后者可通过抑制 Bcl2L12 来恢复。CD4 T 细胞中的 Bcl2L12 可能是治疗 AR 和其他过敏疾病的新靶点。
