Interleukin-2/anti-interleukin-2 complex attenuates inflammation in a mouse COPD model by expanding CD4+ CD25+ Foxp3+ regulatory T cells

• Published in: International immunopharmacology 2024-04, Vol.131, p.111849-111849, Article 111849
• Main Authors: Duan, Ruirui, Huang, Ke, Yu, Tao, Chang, Chenli, Chu, Xu, Huang, Yuhang, Zheng, Zhoude, Ma, Linxi, Li, Baicun, Yang, Ting
• Format: Article
• Language: English
• Subjects: Chronic obstructive pulmonary disease; Inflammation; Interleukin-2/anti-interleukin-2 complex; Regulatory T cells
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2024.111849

•COPD is the leading cause of death worldwide, and there is currently no cure.•The IL-2 immune complex (IL-2C) can selectively induce the expansion of Tregs.•IL-2C alleviates COPD development by inducing Tregs in a mouse model.•Treg expansion is the primary mechanism mediating the beneficial effects of IL-2C on lung inflammation.•Treatment with IL-2C in lieu of adoptive immunotherapy may be an effective therapy for COPD. Chronic, nonspecific inflammation of the alveoli and airways is an important pathological feature of chronic obstructive pulmonary disease (COPD), while sustained inflammatory reactions can cause alveolar damage. Regulatory T cells (Tregs) inhibit inflammation, whereas the interleukin-2/anti-interleukin-2 complex (IL-2C) increases the number of Tregs; however, whether the IL-2C has a therapeutic role in COPD remains unknown. Therefore, this study investigated whether IL-2C alleviates lung inflammation in COPD by increasing the number of Tregs. A mouse COPD model was created by exposing mice to lipopolysaccharides (LPS) and cigarette smoke (CS), and the effects of IL-2C treatment on COPD were evaluated. The number of Tregs in the spleen and lung, pulmonary pathological changes, and inflammatory damage were examined through flow cytometry, histopathology, and immunofluorescence, respectively. IL-2C increased the number of Treg cells in the spleen and lungs after exposure to CS and LPS, reduced the number of T helper 17 (Th17) cells in lung tissue, and improved the Th17/Treg balance. IL-2C decreased the number of inflammatory cells and reduced the levels of pro-inflammatory cytokines IL-6, TNF-α, IL-1β, CCL5, KC, and MCP-1 in bronchoalveolar lavage fluid and serum. IL-2C significantly reduced the pathological scores for lung inflammation, as well as decreased airway mucus secretion and infiltration of neutrophils and macrophages in the lungs. The depletion of Tregs using anti-CD25 antibodies eliminated the beneficial effects of IL-2C. IL-2C is a potential therapeutic agent for alleviating excessive inflammation in the lungs of patients with COPD.