Coinhibitory Molecule VISTA Play an Important Negative Regulatory Role in the Immunopathology of Bronchial Asthma

Jianqun Yin,&ast; Jiawei Chen,&ast; Ting Wang, Huiming Sun, Yongdong Yan, Canhong Zhu, Li Huang, Zhengrong Chen Respiratory Department, Children’s Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengrong Chen; Li Huang, Respiratory Department, Children’s Hospital of Soochow University, No. 303 Jingde Road, Gusu District, Suzhou City, Jiangsu Province, People’s Republic of China, Tel +86-13771721180 ; +86-18962183510, Email chenzhengrong@suda.edu.cn; huanglilcy@163.comObjective: To investigate the significance of VISTA in bronchial asthma and its impact on the disease.Methods: Human peripheral blood of asthma children was gathered. The expression concentrations of VISTA, IL-4, IL-6, CD25, CD40L, and PD-L2 in peripheral blood plasma were detected by ELISA. We established the mouse model of asthma and intervened with agonistic anti-VISTA mAb (4C11) and VISTA fusion protein. ELISA, flow cytometry, and Western blotting were performed to detect the expression levels of Th1, Th2, and Th17 cell subsets and related characteristic cytokines, as well as the protein levels of MAPKs, NF-κB, and TRAF6 in lung tissues. In addition, the infiltration of eosinophils and inflammatory cells, airway mucus secretion, and VISTA protein expression in lung histopathological sections of different groups of mice were analyzed.Results: The concentration of VISTA in human asthma group decreased significantly (p < 0.05); A positive correlation was observed between VISTA and CD40L. The intervention of 4C11 mAb and fusion protein respectively during the induction period increase the differentiation of Th1 cells and the secretion of IFN-γ, and inhibit the differentiation of Th2 and Th17 cells, as well as the secretion of IL-4, IL-5, IL-13 and IL-17, partially reduce the pathological changes of asthma in mouse lungs and correct the progress of asthma. The MAPK, NF-κB, and TRAF6 protein levels were the middle range in the 4C11 mAb and fusion protein groups (p < 0.05).Conclusion: The findings suggest VISTA may play a negative regulatory role in the occurrence and development of bronchial asthma.Keywords: VISTA, bronchial asthma, Th2 cells, cytokines, anti-VISTA mAb, VISTA fusion protein