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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 VGVAPGinduced 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.
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https://hal.univ-reims.fr/hal-03170597
Contributor : Valerian Dormoy <>
Submitted on : Tuesday, March 16, 2021 - 12:10:48 PM
Last modification on : Monday, May 17, 2021 - 2:52:24 PM
Long-term archiving on: : Thursday, June 17, 2021 - 7:26:33 PM

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Flora Lemaire, Sandra Audonnet, Jeanne-Marie Perotin, Pierre Gaudry, Sandra Dury, et al.. The elastin peptide VGVAPG increases CD4+ T-cell IL-4 production in patients with chronic obstructive pulmonary disease. Respiratory Research, BioMed Central, 2021, 22 (1), ⟨10.1186/s12931-020-01609-4⟩. ⟨hal-03170597⟩

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