Biologic treatment specifically increases resting regulatory T-cells (Tregs) in blood of patients with severe asthma

<bold>Background:</bold> Regulatory T-cells (Tregs) can have anti-inflammatory properties. Effects of biologics on specific Treg subpopulations in severe asthma are poorly understood. <bold>Methods:</bold> Patients with severe asthma were either treated with antibodies targeting the Interleukin-(IL)-5 pathway (Mepolizumab or Benralizumab) or an antibody targeting the IL-4/13 pathway (Dupilumab). Total Tregs (CD3+CD4+FoxP3+) and Treg subpopulations in blood were analysed using flow cytometry at baseline, and after 1, 6, 12 months of treatment. In addition, controls without asthma were analysed. <bold>Results:</bold> Seventeen patients were treated with Mepolizumab/Benralizumab (medians at baseline: age 56 years; 1040 eosinophils/µl; FeNO 67 ppb; total IgE 364 IU/l) and 14 patients with Dupilumab (medians at baseline: age 59 years; 455 eosinophils/µl; FeNO 65 ppb; total IgE 413 IU/l). In both patient groups, biologic treatment led to strong improvements in asthma control and exacerbation rates. There were no significant differences in total Tregs or Treg subpopulations between controls and the 2 groups of patients with severe asthma at baseline. Both biologic treatments led to significant increases in resting Tregs (CD3+CD4+FoxP3+CD45RA+)(medians at baseline, 6 months and 12 months of treatment: in the Mepolizumab/Benralizumab group 9 cells/µl, 18 cells/µl, 27 cells/µl; in the Dupilumab group 11 cells/µl, 24 cells/µl, 19 cells/µl). In contrast, there were no significant changes in the total number of Tregs or other Treg subpopulations in blood during the treatment period. <bold>Conclusion:</bold> Biologic treatment of patients with severe asthma is associated with a specific increase in resting Tregs in blood.