The elastin peptide VGVAPG increases CD4+ T-cell IL-4 production in patients with chronic obstructive pulmonary disease.

Abstract

BACKGROUND:

In chronic obstructive pulmonary disease (COPD), lung-infiltrating inflammatory cells secrete proteases and participate in elastin breakdown and genesis of elastin-derived peptides (EP). In the present study, we hypothesized that the pattern of T lymphocytes cytokine expression may be modulated by EP in COPD patients.

METHODS:

CD4+ and CD8+ T-cells, sorted from peripheral blood mononuclear cells (PBMC) collected from COPD patients (n = 29) and controls (n = 13) were cultured with or without EP. Cytokine expression in T-cell phenotypes was analyzed by multicolor flow cytometry, whereas desmosine concentration, a specific marker of elastin degradation, was measured in sera.

RESULTS:

Compared with control, the percentage of IL-4 (Th2) producing CD4+ T-cells was decreased in COPD patients (35.3 ± 3.4% and 26.3 ± 2.4%, respectively, p < 0.05), whereas no significant differences were found with IFN-γ (Th1) and IL-17A (Th17). Among COPD patients, two subpopulations were observed based on the percentage of IL-4 (Th2) producing CD4+ T-cells, of which only one expressed high IL-4 levels in association with high levels of desmosine and strong smoking exposure (n = 7). Upon stimulation with VGVAPG, a bioactive EP motif, the percentage of CD4+ T cells expressing IL-4 significantly increased in COPD patients (p < 0.05), but not in controls. The VGVAPG-induced increase in IL-4 was inhibited in the presence of analogous peptide antagonizing VGVAPG/elastin receptor (S-gal) interactions.

CONCLUSIONS:

The present study demonstrates that the VGVAPG elastin peptide modulates CD4+ T-cells IL-4 production in COPD. Monitoring IL-4 in circulating CD4+ T-cells may help to better characterize COPD phenotypes and could open a new pharmacologic opportunity through CD4+ T-cells stimulation via the VGVAPG/S-gal receptor in order to favor an anti-inflammatory response in those COPD patients.

• Authors: Flora Lemaire, Sandra Audonnet, Jeanne-Marie Perotin, Pierre Gaudry, Sandra Dury, Julien Ancel, François Lebargy, Frank Antonicelli, Gaëtan Deslée, Richard Le Naour
• Journal: Respiratory research (Respir Res) Vol. 22 Issue 1 Pg. 14 (Jan 13 2021) ISSN: 1465-993X [Electronic] England
• PMID: 33435988 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• IL4 protein, human
• Oligopeptides
• Interleukin-4
• valyl-glycyl-valyl-alanyl-prolyl-glycine

Topics

• Adult
• Aged
• CD4-Positive T-Lymphocytes (drug effects, immunology, metabolism)
• Cells, Cultured
• Female
• Humans
• Interleukin-4 (blood)
• Leukocytes, Mononuclear (drug effects, immunology, metabolism)
• Male
• Middle Aged
• Oligopeptides (pharmacology)
• Pulmonary Disease, Chronic Obstructive (blood, immunology)