ICS/LABA Combined With Subcutaneous Immunotherapy Modulates the Th17/Treg Imbalance in Asthmatic Children

RationaleThe imbalance of T helper (Th17) cell and regulatory T (Treg) cell are involved in allergic asthma pathogenesis. We hypothesized that ICS/LABA could modulate the Th17/Treg imbalance and that subcutaneous immunotherapy (SCIT) could coordinate with ICS/LABA to rebalance the dysfunction of Th17/Treg. MethodsThirty house dust mites (HDM) allergic asthmatic children and fifteen healthy control subjects were enrolled in this study. Fifteen asthmatic children were treated by ICS/LABA powder inhalation, while the other fifteen asthmatic children were treated by ICS/LABA powder inhalation combined with HDM-SCIT. Asthmatic subjects were followed up for 6 months, but 2 asthmatics treated with ICS/LABA were lost to follow-up. Flow cytometry was used to determine the proportions of Th17 and Treg in CD4(+) T cells from peripheral blood mononuclear cells (PBMCs). Serum levels of IL-17A and IL-10 were assessed by ELISA. ResultICS/LABA treatment significantly reduced the percentage of Th17 cells (1.252 +/- 0.134% vs. 2.567 +/- 0.386%), serum IL-17A (49.42 +/- 2.643 pg/ml vs. 66.75 +/- 3.442 pg/ml) and Th17/Treg ratio (0.194 +/- 0.025 vs. 0.439 +/- 0.072) compared to baseline (P<0.01). The ICS/LABA+HDM-SCIT treatment group showed similar reduction in the percentage of Th17 cells (1.11 +/- 0.114% vs. 2.654 +/- 0.276%), serum IL-17A (49.23 +/- 2.131 pg/ml vs. 66.41 +/- 2.616 pg/ml) and the Th17/Treg ratio (0.133 +/- 0.015 vs. 0.4193 +/- 0.050) (P<0.01). ICS/LABA+HDM-SCIT treatment group demonstrated elevated Treg percentages (8.483 +/- 0.408% vs. 6.549 +/- 0.299%) and serum IL-10 levels (127.4 +/- 4.423 pg/ml vs. 93.15 +/- 4.046 pg/ml), resulting in a lower Th17/Treg ratio than the ICS/LABA group. ConclusionICS/LABA treatment regulates Th17/Treg imbalance mainly by mitigating Th17-induced inflammation in asthma patients. The addition of SCIT further enhanced such effect by upregulating Treg cells.

Automated summary

The study demonstrates that ICS/LABA and SCIT therapies can significantly improve the Th17/Treg imbalance in asthma patients, reducing the percentage of Th17 cells and serum IL-17A levels, while increasing the proportion of Treg cells. These findings suggest new approaches for treating asthma.