胸腺基质淋巴细胞生成素
免疫球蛋白E
免疫学
过敏性炎症
卵清蛋白
CXCR5型
间质细胞
白细胞介素4
化学
生物
细胞生物学
炎症
免疫系统
抗体
癌症研究
B细胞
生发中心
作者
Minghui Xue,Shuqin Xu,Li Su,S. He,Bing Wu,Cunpeng Ji,Lin Lin,Xin Nie,Gang Cai
标识
DOI:10.1016/j.clim.2021.108822
摘要
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.
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