Clinical Immunology ( IF 4.5 ) Pub Date : 2021-08-13 , DOI: 10.1016/j.clim.2021.108822 Minghui Xue 1 , Shuqin Xu 1 , Li Su 2 , Siwei He 1 , Beiying Wu 1 , Cunpeng Ji 3 , Lin Lin 1 , Xiaomeng Nie 4 , Gang Cai 1
Lung surfactant protein A (SP-A) is critical for immunomodulation. Thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) drive T follicular helper (Tfh) cells differentiation in allergic asthma. We employed wild-type (WT) and SP-A−/− mice injected with TSLP and ovalbumin (OVA)-activated DCs and challenged with OVA. Compared with WT mice, we showed that allergic inflammation was dramatically increased in SP-A−/− mice. In parallel, both IL-4-producing CD45RA−CXCR5+PD-1+CD4+ cells (Tfh2) and IgE were markedly increased in SP-A−/− mice. Further study showed that SP-A prohibited TSLP activated-DCs from expressing OX40L. When we blocked OX40L-OX40 and IL-4R signaling, the differentiation of Tfh2 and IgE responses in SP-A−/− mice was significantly inhibited. In severe asthma patients, SP-A is dysfunctional in modulating the TSLP-DCs-mediated differentiation of Tfh cells. This study suggests that SP-A acts as a modulator of Tfh differentiation and IgE generation in asthma.
中文翻译:
表面活性剂蛋白-A 抑制哮喘中胸腺基质淋巴细胞生成素介导的 T 滤泡辅助细胞分化和 IgE 产生
肺表面活性蛋白 A (SP-A) 对免疫调节至关重要。胸腺基质淋巴细胞生成素 (TSLP) 激活的树突状细胞 (DC) 在过敏性哮喘中驱动 T 滤泡辅助 (Tfh) 细胞分化。我们使用注射了 TSLP 和卵清蛋白 (OVA) 激活的 DC 并用 OVA 攻击的野生型 (WT) 和 SP-A -/-小鼠。与WT小鼠相比,我们发现SP-A -/-小鼠的过敏性炎症显着增加。同时,产生 IL-4 的 CD45RA - CXCR5 + PD-1 + CD4 +细胞 (Tfh2) 和 IgE 在 SP-A -/-中显着增加老鼠。进一步的研究表明,SP-A 禁止 TSLP 激活的 DCs 表达 OX40L。当我们阻断 OX40L-OX40 和 IL-4R 信号时,SP-A -/-小鼠中 Tfh2 和 IgE 反应的分化被显着抑制。在严重哮喘患者中,SP-A 在调节 TSLP-DCs 介导的 Tfh 细胞分化方面功能失调。该研究表明,SP-A 可作为哮喘中 Tfh 分化和 IgE 生成的调节剂。