Intervention with ICOSL Antibodies Alleviates Inflammatory Infiltrations in Mice with Neutrophilic Asthma

• Published in: Iranian journal of immunology Vol. 21; no. 1; pp. 53 - 64
• Main Authors: Dong, Heting, Ren, Yinying, Song, Yiyi, Ji, Wei, Yan, Yongdong, Zhu, Canhong, Huang, Li, Wang, Meijuan, Gu, Wenjing, Zhang, Xinxing, Sun, Huiming, Hao, Chuangli, Chen, Zhengrong
• Format: Journal Article
• Language: English
• Published: Iran Shiraz Institute for Cancer Research 12-03-2024
• Subjects: Asthma; Bronchus; Enzyme-linked immunosorbent assay; Helper cells; Immunoglobulin G; Infiltration; Inflammation; Lavage; Leukocytes (neutrophilic); Lipopolysaccharides; Lymphocytes T; Mucus; Neutrophils; Ovalbumin; Respiratory tract diseases; γ-Interferon; Pathology; Inducible T Cell Co-Stimulator Ligand; Neutrophils; Asthma
• ISSN: 1735-1383; 1735-367X
• DOI: 10.22034/iji.2024.98853.2594

Neutrophilic asthma is characterized by the predominant infiltration of neutrophils in airway inflammation.
To explore the therapeutic potential of an antibody against the inducible T cell co-stimulator ligand (ICOSL) in a mouse model of neutrophilic asthma.
Female BALB/c mice were randomly assigned to different groups. They were then injected with ovalbumin (OVA)/lipopolysaccharides (LPS) to induce neutrophilic asthma. The mice were then treated with either anti-ICOSL (the I group), control IgG (the G group), or no treatment (the N group). Additionally, a control group of mice received vehicle PBS and was labeled as the C group (n=6 per group). One day after the last allergen exposure, cytokine levels were measured in plasma and bronchoalveolar lavage fluid (BALF) using ELISA. After analyzing and categorizing BALF cells, the lung tissues were examined histologically and immunohistochemically.
Administering anti-ICOSL resulted in a significant decrease in the total number of inflammatory infiltrates and neutrophils found in BALF. Moreover, it led to a decrease in the levels of interleukin (IL)-6, IL-13, and IL-17 in both BALF and plasma. Additionally, there was an increase in IFN-γ levels in the BALF of asthmatic mice (p<0.05 for all). Treatment with anti-ICOSL also reduced lung interstitial inflammation, mucus secretion, and ICOSL expression in asthmatic mice.
The treatment of anti-ICOSL effectively improved lung interstitial inflammation and mucus secretion in mice with neutrophilic asthma by restoring the balance of Th1/Th2/Th17 responses. These findings indicate that blocking the ICOS/ICOSL signaling could be an effective way to manage neutrophilic asthma.