Glucagon-like peptide-1 receptor (GLP-1R) signaling ameliorates dysfunctional immunity in COPD patients

• Published in: International journal of chronic obstructive pulmonary disease Vol. 13; pp. 3191 - 3202
• Main Authors: Huang, Jingwen, Yi, Huahua, Zhao, Chunliu, Zhang, Yifan, Zhu, Liying, Liu, Bing, He, Ping, Zhou, Min
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2018; Dove Medical Press Ltd; Dove Medical Press
• Subjects: Analysis; Anti-inflammatory agents; Antibodies; Antigens; Apoptosis; Biological response modifiers; Cell death; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Cytokines - blood; Dehydrogenases; Diabetes therapy; EDTA; Female; Flow cytometry; Gene expression; Gene Expression Profiling - methods; Glucagon; Glucagon-like peptide-1 receptor; Glucagon-Like Peptide-1 Receptor - genetics; Glucagon-Like Peptide-1 Receptor - immunology; Health aspects; Humans; Immunologic Factors - pharmacology; Infections; Inflammation; Inflammation - metabolism; Insulin; interferon-; Interferon-gamma - genetics; Leukocytes, Mononuclear - immunology; Liraglutide; Liraglutide - pharmacology; Lymphocytes; Male; Medical schools; Metabolism; Middle Aged; Original Research; Oxidative stress; Oxidative Stress - immunology; Peptide Fragments - genetics; Peptides; Programmed Cell Death 1 Receptor - genetics; Proteins; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - immunology; Pulmonary Disease, Chronic Obstructive - metabolism; Respiratory system agents; Signal Transduction; Smoking - immunology; Smoking - metabolism; T cells; T-cell; Tumor necrosis factor-TNF; Up-Regulation - drug effects; United States > US; liraglutide; interferon-γ; T cell; glucagon-like peptide-1 receptor; COPD
• ISSN: 1178-2005; 1176-9106; 1178-2005
• DOI: 10.2147/COPD.S175145

The glucagon-like peptide-1 receptor (GLP-1R) agonist - liraglutide (LIR) - is an insulin secretagogue for the treatment of diabetes and has been proven to have therapeutic potential in the treatment of COPD. Evidence suggested that activating GLP-1R signaling might have immunomodulating and anti-inflammatory effects. COPD is characterized by dysregulation of immunity, oxidative stress, and excessive inflammation responses. The aim of this study was to investigate whether GLP-1R signaling had a regulatory role in COPD immunity. Fifty-seven COPD patients in a stable condition and 51 age-, sex-, and smoking history-matched non-COPD subjects provided blood samples for isolation of peripheral blood mononuclear cells (PBMCs). GLP-1R expression was measured, and its association with clinical parameters and plasma cytokines was analyzed. T cell function was assessed at baseline and after regulating GLP-1R expression. GLP-1R expression decreased in circulating PBMCs of COPD patients, which was associated with decreased interferon (IFN)-γ expression. Reduced IFN-γ production stimulated by phytohemagglutinin (PHA) and increased programmed cell death protein 1 (PD-1) expression on T cells were observed in COPD patients compared with non-COPD subjects. Treatment with LIR could upregulate the GLP-1R expression, and this was observed to restore the antigen-stimulated IFN-γ production and downregulate PD-1 expression in T cells. PBMCs of COPD patients showed defective GLP-1R signaling and functional T-lymphocyte abnormalities that could be rescued by LIR treatment.