B Lymphocytes Balance Th1/Th2 to Participate in Fibrotic Hypersensitivity Pneumonia Induced by Pigeon Shedding

We 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.CD19+ 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.The 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.Deleting B lymphocytes or blocking the Notch pathway both reversed the Th1/Th2 imbalance in fibrotic hypersensitivity pneumonia and inhibited pulmonary fibrosis.