The expression and function of programmed death-ligand 1 and related cytokines in neutrophilic asthma

• Published in: Annals of translational medicine Vol. 9; no. 23; p. 1727
• Main Authors: Ren, Yin-Ying, Dong, He-Ting, Liao, Jian-Yi, Sun, Hui-Ming, Wang, Ting, Gu, Wen-Jing, Zhang, Xin-Xing, Yan, Yong-Dong, Ji, Wei, Chen, Zheng-Rong, Zhu, Can-Hong
• Format: Journal Article
• Language: English
• Published: China AME Publishing Company 01.12.2021
• Subjects: Original; Soluble programmed death-ligand 1 (sPD-L1); cytokines; T helper cell type 17/interleukin-17 immunity imbalance (Th17/IL-17 immunity imbalance); murine asthmatic model; neutrophilic asthma (NA)
• ISSN: 2305-5839; 2305-5839
• DOI: 10.21037/atm-21-5648

Programmed death-ligand 1 (PD-L1) is an important immune checkpoint inhibitor. Recent studies suggest that the PD-L1-mediated pathway may be a promising target in allergic asthma. However, the mechanism by which PD-L1 represses neutrophilic asthma (NA) remains unclear. In this study, we examined correlations between the expression of PD-L1 and the production of T helper cell type 1 (Th1), T helper cell type 2 (Th2), and T helper cell type 17 (Th17) cells in pediatric patients with NA and a mouse model. The clinical samples of 26 children with asthma and 15 children with a bronchial foreign body were collected over a period of 12 months by the Children's Hospital of Soochow University. An experimental mouse model of asthma was established to study NA. An enzyme-linked immunoassay (ELISA) was used to assess soluble PD-L1 (sPD-L1) and cytokines [e.g., interleukin (IL)-4, IL-6, interferon gamma (IFN-γ), IL-17 and granulocyte-macrophage colony-stimulating factor (GM-CSF)] in bronchoalveolar lavage fluid (BALF). NA patients had significantly higher levels of sPD-L1, IL-6, IL-17, and GM-CSF in their BALF than non-NA and control patients (P<0.05). In a murine model of asthma, the positive rate and fluorescence intensity of PD-L1 in the NA group and the immunoglobulin G (IgG)-treated NA group were higher than in the PD-L1 antibody (Ab)-treated NA group and the phosphate-buffered saline (PBS) control group (P<0.05). In the plasma and the BALF of the NA group and the IgG-treatment NA group, the levels of IL-17, IL-4, tumor necrosis factor alpha (TNF-α), and granulocyte colony-stimulating were higher than those in the PBS control group (P<0.05). The histopathological examination of lung tissues from all mice groups showed that a large number of inflammatory cells were found around the airway in the NA group and the IgG-treatment group. PD-L1 may contribute to the Th17/IL-17 immune response, which is associated with neutrophilic inflammation and asthma. A PD-L1 blockade reduces pulmonary neutrophils and mucus production.