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

被引:2
作者
Wu, Chao [1 ]
Ding, Wei [1 ]
Li, Yafang [1 ]
Wang, Wenyi [1 ]
Lian, Zhichuang [1 ]
Muhataer, Xirennayi [1 ]
Zhou, Yuan [1 ]
Li, Qifeng [2 ]
Yang, Xiaohong [1 ]
机构
[1] Peoples Hosp Xinjiang Uygur Autonomous Reg, Dept Resp & Crit Care Med, Urumqi, Peoples R China
[2] Childrens Hosp Xinjiang Uygur Autonomous Reg, Xinjiang Inst Pediat, Urumqi, Peoples R China
基金
中国国家自然科学基金;
关键词
Allergic pneumonia; Pigeon breeder's lung; B lymphocytes; Th1; Th2; imbalance; Pulmonary fibrosis; IDIOPATHIC PULMONARY-FIBROSIS; REGULATORY T-CELLS; DENDRITIC CELLS; PERIPHERAL-BLOOD; IL-10; PRODUCTION; BREEDERS LUNG; NOTCH; PATHWAY; METHYLATION; EXPRESSION;
D O I
10.1159/000527533
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Introduction: 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. Methods: 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. Results: 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. Conclusion: Deleting B lymphocytes or blocking the Notch pathway both reversed the Th1/Th2 imbalance in fibrotic hypersensitivity pneumonia and inhibited pulmonary fibrosis.
引用
收藏
页码:122 / 131
页数:10
相关论文
共 39 条
[1]   Notch in T Cell Differentiation: All Things Considered [J].
Amsen, Derk ;
Helbig, Christina ;
Backer, Ronald A. .
TRENDS IN IMMUNOLOGY, 2015, 36 (12) :802-814
[2]   A Systematically Derived Exposure Assessment Instrument for Chronic Hypersensitivity Pneumonitis [J].
Barnes, Hayley ;
Morisset, Julie ;
Molyneaux, Philip ;
Westall, Glen ;
Glaspole, Ian ;
Collard, Harold R. .
CHEST, 2020, 157 (06) :1506-1512
[3]   Developmental pathways in the pathogenesis of lung fibrosis [J].
Chanda, Diptiman ;
Otoupalova, Eva ;
Smith, Samuel R. ;
Volckaert, Thomas ;
De Langhe, Stijn P. ;
Thannickal, Victor J. .
MOLECULAR ASPECTS OF MEDICINE, 2019, 65 :56-69
[4]  
Chen H, 2020, J TRADIT CHIN MED, V40, P204
[5]   IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease [J].
Dambuza, Ivy M. ;
He, Chang ;
Choi, Jin Kyeong ;
Yu, Cheng-Rong ;
Wang, Renxi ;
Mattapallil, Mary J. ;
Wingfield, Paul T. ;
Caspi, Rachel R. ;
Egwuagu, Charles E. .
NATURE COMMUNICATIONS, 2017, 8
[6]   Regulatory B cell: New member of immunosuppressive cell club [J].
Ding, Tingting ;
Yan, Fan ;
Cao, Shui ;
Ren, Xiubao .
HUMAN IMMUNOLOGY, 2015, 76 (09) :615-621
[7]   Adipose-derived mesenchymal stem cells treatments for fibroblasts of fibrotic scar via downregulating TGF-1 and Notch-1 expression enhanced by photobiomodulation therapy [J].
Han, Bing ;
Fan, Jincai ;
Liu, Liqiang ;
Tian, Jia ;
Gan, Cheng ;
Yang, Zengjie ;
Jiao, Hu ;
Zhang, Tiran ;
Liu, Zheng ;
Zhang, Hua .
LASERS IN MEDICAL SCIENCE, 2019, 34 (01) :1-10
[8]   Interleukin-10-producing B-cells in autoimmune bullous diseases [J].
Hashimoto, T. ;
Mizoguchi, A. .
BRITISH JOURNAL OF DERMATOLOGY, 2017, 176 (05) :1119-1120
[9]   A cohort study of interstitial lung diseases in central Denmark [J].
Hyldgaard, Charlotte ;
Hilberg, Ole ;
Muller, Audrey ;
Bendstrup, Elisabeth .
RESPIRATORY MEDICINE, 2014, 108 (05) :793-799
[10]   Mycobacterium tuberculosis (MTB) antigen-induced upregulation of interleukin-35 expression in patients with MTB infection: In vitro blockade of the effects of interleukin-35 on T lymphocyte subsets [J].
Jiang, Hongbin ;
Cui, Beinian ;
Zhang, Jun .
PATHOGENS AND DISEASE, 2021, 79 (06)