Abstract
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.
Highlights
Asthma is a common chronic airway disease in children, and is characterized by airway inflammation, airway hyperresponsiveness (AHR), reversible airflow obstruction and airway remodeling
Fifteen asthmatic children were treated by Inhaled GCs (ICS)/long-acting b2-agonists (LABA) powder inhalation, while the other fifteen asthmatic children were treated by ICS/LABA powder inhalation combined with house dust mites (HDM)-subcutaneous immunotherapy (SCIT)
15 asthmatics were administrated by ICS/LABA treatment and the other 15 asthmatics were administered ICS/LABA treatment combined with SCIT treatment
Summary
Asthma is a common chronic airway disease in children, and is characterized by airway inflammation, airway hyperresponsiveness (AHR), reversible airflow obstruction and airway remodeling. In the long-term exploration of the mechanism and treatment of asthma, glucocorticoids (GCs) have been widely acknowledged as the core therapy for asthma. GCs have direct effects on asthma-related inflammatory cells such as Tlymphocytes, eosinophils, mast cells and dendritic cells [4]. Inhaled GCs (ICS) as single drugs or combined with long-acting b2-agonists (LABA) can directly act on the airway by administration as inhalable liquid or dry powder preparations, which have contributed to obvious benefits in the clinical treatment of asthma. This treatment can not affect underlying immunologic dissonance triggered by allergy
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