Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
Respir Res. 2021 Jun 14;22(1):178. doi: 10.1186/s12931-021-01757-1.
Serine peptidase inhibitor, clade B, member 10 (SERPINB10) contributes to allergic inflammation in asthma. However, its role in the T-helper type 2 (Th2) response of allergic asthma is not known. The goal of this study was to unveil the function of SERPINB10 in the Th2 response of allergic asthma and the mechanism by which SERPINB10 affects the viability of Th2 cells.
Th2 cytokines and serum levels of house dust mite (HDM)-specific IgE in bronchoalveolar lavage fluid were examined by ELISA in an HDM-induced asthma model. The number and apoptosis of Th1 and Th2 cells in mouse lungs were measured by flow cytometry. Naïve CD4 T cells from patients with asthma were cultured under appropriate polarizing conditions to generate Th1 and Th2 cells. SERPINB10 expression in polarized Th1 and Th2 cells was quantified by real-time reverse transcription-quantitative polymerase chain reaction. SERPINB10 expression was knocked down in human CD4 T cells with lentivirus.
Knockdown of SERPINB10 expression significantly diminished HDM-induced Th2 cytokine secretion and level of HDM-specific IgE. After HDM exposure, SERPINB10-knockdown mice had diminished numbers of Th2 cells, but similar numbers of Th1 cells, compared with those in negative-control mice. Th2 cells of SERPINB10-knockdown mice were more susceptible to apoptosis than that of control mice. Stimulating T-cell receptors (TCRs) with anti-CD3 antibody caused upregulation of SERPINB10 expression in polarized Th2 cells, but not polarized Th1 cells. Knockdown of SERPINB10 expression resulted in fewer numbers and greater apoptosis of polarized Th2 cells.
Our results suggest that SERPINB10 may contribute to allergic inflammation and the Th2 response of asthma by inhibiting the apoptosis of Th2 cells.
丝氨酸蛋白酶抑制剂，B 族，成员 10（SERPINB10）可导致哮喘中的过敏炎症。然而，其在过敏性哮喘的 T 辅助型 2（Th2）反应中的作用尚不清楚。本研究旨在揭示 SERPINB10 在过敏性哮喘 Th2 反应中的作用，以及 SERPINB10 影响 Th2 细胞活力的机制。
通过酶联免疫吸附试验（ELISA）在屋尘螨（HDM）诱导的哮喘模型中检测支气管肺泡灌洗液中的 Th2 细胞因子和血清 HDM 特异性 IgE 水平。通过流式细胞术测量小鼠肺部 Th1 和 Th2 细胞的数量和凋亡。从哮喘患者的幼稚 CD4 T 细胞在适当的极化条件下培养以生成 Th1 和 Th2 细胞。通过实时逆转录定量聚合酶链反应定量极化 Th1 和 Th2 细胞中的 SERPINB10 表达。使用慢病毒敲低人 CD4 T 细胞中的 SERPINB10 表达。
敲低 SERPINB10 表达显著降低了 HDM 诱导的 Th2 细胞因子分泌和 HDM 特异性 IgE 水平。与阴性对照小鼠相比，在暴露于 HDM 后，SERPINB10 敲低小鼠的 Th2 细胞数量减少，但 Th1 细胞数量相似。SERPINB10 敲低小鼠的 Th2 细胞比对照小鼠更易凋亡。用抗 CD3 抗体刺激 T 细胞受体（TCRs）导致极化 Th2 细胞中 SERPINB10 表达上调，但不导致极化 Th1 细胞中 SERPINB10 表达上调。敲低 SERPINB10 表达导致极化 Th2 细胞数量减少和凋亡增加。
我们的结果表明，SERPINB10 可能通过抑制 Th2 细胞凋亡来促进过敏炎症和哮喘的 Th2 反应。
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