Glucagon-like peptide-1 receptor (GLP-1R) signaling ameliorates dysfunctional immunity in COPD patients
Received 23 May 2018
Accepted for publication 21 August 2018
Published 9 October 2018 Volume 2018:13 Pages 3191—3202
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Chunxue Bai
Jingwen Huang,1,* Huahua Yi,1,* Chunliu Zhao,2 Yifan Zhang,3 Liying Zhu,3 Bing Liu,1 Ping He,4 Min Zhou1
1Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Respiratory Medicine, Luwan Branch, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Microbiology and Immunology, Institutes of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
*These authors contributed equally to this work
Background: 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.
Patients and methods: 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.
Results: 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.
Conclusion: PBMCs of COPD patients showed defective GLP-1R signaling and functional T-lymphocyte abnormalities that could be rescued by LIR treatment.
Keywords: COPD, glucagon-like peptide-1 receptor, liraglutide, interferon-γ, T cell
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