Immunoregulatory Effects of Subcutaneous Immunotherapy on Lymphocyte Subgroups and Cytokines in Children with Asthma

Abstract

Objective Asthma is a syndrome that incorporates many immune phenotypes. The immunologic effects of subcutaneous immunotherapy (SCIT) exerts on allergic asthma remain still largely unknown. Here, we investigated the effects of SCIT on cytokine production and peripheral blood levels of lymphocyte subtypes in children with mite-induced moderate and severe allergic asthma. Methods The study included 60 kids with mite-induced allergic asthma from 5 to 10 years old. All subjects had received antiasthmatic pharmacologic for 3 months at baseline. Half of the children were treated with SCIT combined with pharmacologic treatment named the SCIT group and the other half only with pharmacologic therapy named the no-SCIT group. Total asthma symptom score (TASS) and total medication score (TMS) were recorded. Flow cytometry was used to identify lymphocyte subtypes: type 2 innate lymphocytes (ILC2s), type 1 (Th1) and type 2 (Th2) helper T cells, T helper 17 (Th17) cells, and regulatory T (Treg) cells. ELISA, flow cytometry, and cytometric bead array were used to assess cytokines IL-13, IFN-γ, IL-4, IL-17, and TGF-β, at baseline and 3 and 6 months after study treatment in both groups of patients. Results Both groups can significantly improve clinical symptoms in children with asthma. SCIT can significantly reduce asthma medication after 6 months of treatment. SCIT induced a significantly higher and progressive reduction in ILC2 percentage and IL-13 levels after 3 and 6 months of treatment compared with baseline and compared with no-SCIT patients. Significant differences were detected in the Th1/Th2 cell ratio and IFN-γ/IL-4 cytokine ratio between groups after 6 months of treatment. Similarly, the Th17/Treg ratio and IL-17/TGF-β ratio in the SCIT group were much lower than those in the no-SCIT group after 3-6 months of treatment. Conclusion SCIT is a promising option to reduce the percentage of ILC2 and regulate Th1/Th2 and Th17/Treg immune balance in the peripheral blood of children with asthma.

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“…134 In patients with asthma, blood ILC2 frequency and IL-13 levels were reduced with SCIT and pharmacotherapy compared with pharmacotherapy alone. 135 Significant decreases in circulating ILC2 numbers were observed in newly diagnosed patients with asthma after budesonide treatment. 113 Budesonide also inhibited phosphorylation of signal transducer and activator of transcription proteins and JAK3 and greatly reduced type 2 cytokine production from ILC2s in vitro.…”

Critical Roles of Balanced T Helper 9 Cells and Regulatory T Cells in Allergic Airway Inflammation and Tumor Immunity

“…Genetic and immunological evidence indicates that Treg cells play pivotal roles in promoting tolerance to allergens and preventing allergic asthma [139]. Moreover, a number of studies have investigated associations of impaired function and decreased frequencies of Treg cells with the development of allergic asthma [140][141][142]. Adoptive transfer of antigenspecific Treg cells suppressed allergic inflammation and airway hyperreactivity in asthmatic mice [143].…”

Regulatory T cells mediated immunomodulation during asthma: a therapeutic standpoint

“…These studies emphasized that the reconstitution of antigen-specific FOXP3 + Tregs was found to subdue allergic inflammatory responses and hyper reactivity via the IL-10 dependent pathway [33,81,101], and further downregulated established inflammation and prevent airway remodeling when injected after disease onset [102]. The therapeutic application of Tregs has been tested in clinical and preclinical platforms to achieve desired immunosuppression and to suppress asthma inflammation [89,[102][103][104][105][106][107].…”