Chronic Pseudomonas aeruginosa lung infection, but not CFTR modulator therapy affects circulating regulatory T cells in an adult population with cystic fibrosis

Abstract

<b>Background:</b> Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene which is expressed in epithelial-line cells, but also in immune cells. Reported T cell abnormalities in CF include dysregulated Th2/Th17 cells and an impairment of regulatory T cells (Tregs). <b>Aims and objectives:</b> We hypothesized that there would be effects on the composition of lymphocyte subsets in patients with CF (PWCF) receiving CFTR modulators. <b>Methods:</b> Peripheral blood mononuclear cells and serum samples were collected from 108 PWCF and 40 patients with non-CF bronchiectasis between March and October 2020. Samples were analysed for peripheral blood lymphocytes subsets and systemic T helper cell-associated cytokines using flow cytometry. <b>Results:</b> 55/108 (51%) of PWCF received either mono or dual-combination CFTR modulator therapy. There were no differences in proportions of analysed T cell subsets or cytokines between PWCF who were versus were not receiving CFTR modulators. Additional analysis revealed lower percentages of Tregs in PWCF with chronic Pseudomonas aeruginosa lung infection (8.2% vs. 7.5% of T helper cells, p=0.028). This effect was not observed in patients with non-CF bronchiectasis. Tregs with CD39 expression were higher in patients with non-CF bronchiectasis versus PWCF (60.2% vs. 50.4% of Tregs; p&lt;0.001). Patients with non-CF bronchiectasis tended to have higher percentages of Th2- and Th17-cells and higher levels of peripheral cytokines versus PWCF. <b>Conclusions:</b> Chronic Pseudomonas aeruginosa lung infection appears to impair Tregs in PWCF-a phenomenon that is potentially specific to CF.