B Lymphocytes Balance Th1/Th2 to Participate in Fibrotic Hypersensitivity Pneumonia Induced by Pigeon Shedding
B Lymphocytes Balance Th1/Th2 to Participate in Fibrotic Hypersensitivity Pneumonia Induced by Pigeon Shedding
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DOI：
10.1159/000527533
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发表时间：
2022-11-02
影响因子：
2.8
通讯作者：
Yang，Xiaohong
中科院分区：
文献类型：
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作者：
Wu，Chao;Ding，Wei;Yang，Xiaohong
目的探讨B淋巴细胞调节Th 1/Th 2失衡参与鸽散毒致敏性肺炎大鼠肺纤维化的分子机制。DAPT用于抑制Notch信号通路。HE及Masson染色观察病理改变。Western blot检测蛋白水平。流式细胞仪检测Th 1/Th 2比值。结果CD 19 −大鼠肺纤维化病理改变不明显，DAPT治疗后肺纤维化病理改变不明显。模型组大鼠肺组织中Notch信号通路蛋白Notch 1、Notch 2、Jag 1、Jag 2、DLL 1和DLL 4均较对照组显著上调。然而，这些蛋白质在CD 19 −大鼠中低于CD 19+大鼠，表明B细胞在诱导肺炎中起关键作用。模型组大鼠BALF中Th 1/Th 2比值降低，DAPT可进一步逆转模型组大鼠BALF中Th 1/Th 2比值的降低。然而，我们发现，在CD 19 −大鼠，调节的Th 1/Th 2比值的Notch信号通路是losed.Conclusiondeleting B淋巴细胞或阻断Notch途径都逆转了Th 1/Th 2失衡的纤维化过敏性肺炎和抑制肺纤维化。
IntroductionWe investigated the molecular mechanism by which B lymphocytes regulate Th1/Th2 imbalance to participate in the pulmonary fibrosis in hypersensitivity pneumonia induced by pigeon shedding in rats.MethodsCD19+ rats and CD19− rats were used to construct animal models of fibrotic hypersensitivity pneumonia. DAPT was used to inhibit the Notch signaling pathway. The pathological changes were assessed with HE and Masson staining. Protein level was detected with Western blot. Th1/Th2 ratio was analyzed with flow cytometry. Cytokine levels were measured with ELISA.ResultsThe pathological changes of pulmonary fibrosis were not obvious in the CD19− rats and after DAPT treatment. Notch signaling pathway proteins, including Notch1, Notch2, Jag1, Jag2, DLL1, and DLL4, in lung tissues of model rats were all significantly upregulated than those in control rats. However, these proteins in CD19− rats were lower in CD19+ rats, suggesting that B cells play a key role in inducing pneumonia. Besides, the Th1/Th2 ratio in the BALF of model rats decreased, which was further reversed by DAPT. However, we found that in CD19− rats, the regulation of the Th1/Th2 ratio by the Notch signaling pathway was lost.ConclusionDeleting B lymphocytes or blocking the Notch pathway both reversed the Th1/Th2 imbalance in fibrotic hypersensitivity pneumonia and inhibited pulmonary fibrosis.