Investigation of immune dysregulation in bronchiectasis: alterations of myeloid-derived suppressor cells and regulatory T cells

<bold>Background:</bold> Cole’s vicious vortex and immune dysregulation hold a central role in the pathogenesis of bronchiectasis. HLA-DRlowCD11b+CD33+ myeloid-derived suppressor cells (MDSCs) and CD4+CD25highFOXP3+ regulatory T cells (Tregs) mainly act through suppression of T-cell responses, while their role in bronchiectasis is still unknown. <bold>Aims and Objectives:</bold> The study aimed to investigate the alterations of MDSCs and Tregs in the immune dysregulation that characterises bronchiectasis and compare them with clinical, laboratory, and imaging features and disease outcomes. <bold>Methods:</bold> MDSCs and Tregs from the fraction of peripheral blood mononuclear cells (PBMCs) in 40 bronchiectasis patients and 30 healthy controls were measured by flow cytometry and expressed as percentages of PBMCs. Clinical and laboratory data, QOL-B, BRICS, BSI, and FACED scores were collected from all patients. <bold>Results:</bold> The patients presented increased MDSCs (8.34%±8.18) and decreased Tregs (0.56%±0.98) compared to controls (3.72%±3.47, p=0.0061 and 0.90%±0.83, p=0.0315, respectively, Mann–Whitney U test), without significant differences among the underlying causes of bronchiectasis (p=0.3419 and p=0.6820, respectively, Kruskall–Wallis test). In the patients, MDSCs were correlated to CRP levels (r=0.5151, p=0.0011, Spearman) and inversely correlated to FEV1 (r=-0.4372, p=0.0048, Spearman) and FVC (r=-0.3874, p=0.0135, Spearman) percentage of predicted. <bold>Conclusions:</bold> Immunomodulatory cell populations are altered in bronchiectasis and constitute promising novel biomarkers of disease severity, as their counts are correlated to inflammatory and pulmonary function markers. *AMM & NB contributed equally