Increased pro-inflammatory cytokine-secreting regulatory T cells are correlated with the plasticity of T helper cell differentiation and reflect disease status in asthma

Background: Human regulatory T cells (Tregs) are a heterogeneous population which consists of three distinct subpopulations: CD25(+)CD45RA(+) resting Treg (rTreg) cells; CD25(hi)CD45RA(-) activated Treg (aTreg) cells, which are both suppressive; and CD25(+)CD45RA(-) cytokine-secreting T cells with pro-inflammatory capacity. Objective: We investigated variation in peripheral Treg subpopulations of asthma and explored their potential roles in asthma inflammation. Methods: Twenty-eight mild asthma patients, 26 moderate asthma patients, 18 severe asthma patients, and 36 healthy controls were recruited for a cross-sectional study. Phenotyping of peripheral CD4(+) Tregs was performed based on flow cytometry results. Results: The proportions of rTreg and aTreg cells among CD4(+) T cells were higher in mild and moderate asthma patients than in healthy controls. All three groups of asthmatics had a higher proportion of pro-inflammatory Tregs than healthy controls, and these increased with asthma severity. The proportion of IL-17-producing Foxp3(+) cells and IFN-gamma-producing Foxp3(+) cells strongly correlated with T helper 17 (Th17) cells (r = 0.66, p < 0.001) and Thl cells (r = 0.48, p < 0.001). The pro-inflammatory Treg subpopulation was correlated with the severity of asthma and may be insensitive to corticosteroids. Conclusions: Our data suggest that pro-inflammatory Treg subpopulations may be relevant to the plasticity of Th17 and Th1 differentiation and play an important role in the pathogenesis of asthma.