Abstract
Objective: Allergic asthma is a chronic airway inflammation resulting from an imbalance of T helper (Th) cell responses to allergens. Interleukin (IL)-35 has been shown to have potent immunoregulatory properties. Whether IL-35 participates in the immunopathogenesis of allergic asthma patients is still unknown. Methods: CD4+ T cells and CD4+CD25− T cells were obtained from peripheral blood mononuclear cells (PBMCs) using magnetic separation. The concentration of IL-35 in plasma was measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of the IL-35 subunits, EBI3 and IL-12p35, were detected by quantitative real-time PCR (qPCR). The proliferative responses of CFSE-labeled CD4+CD25− T cells in the presence or absence of rhIL-35 were evaluated by flow cytometry. Cytokine production of activated CD4+CD25− T cells was examined by flow cytometry and ELISA. Results: IL-35 protein and mRNA levels were decreased in allergic asthmatics. The frequencies of CD4+CD25+Foxp3+ Tregs and CD4+IL-12p35+ T cells in allergic asthma patients were lower than in healthy controls. Moreover, the addition of rhIL-35 suppressed CFSE+CD4+CD25− T cell proliferation in vitro in a dose-dependent manner, and the suppression induced by rhIL-35 was associated with decreases in IL-4 but not IFN-γ and IL-17 production of activated CD4+CD25− T cells. The increased level of Th1/Th2 was observed in allergic asthmatics in the presence of rhIL-35. Conclusions: Our data suggest that IL-35 can effectively suppress the proliferation and IL-4 production of activated CD4+CD25− T cells in allergic asthma, and that IL-35 may be a new immunotherapy for asthma patients.
Acknowledgements
We thank Dr. Yuhui Lin for recruiting allergic asthma patients. We thank all the blood donors participating in this study.
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. The research was supported by the grants from the National Natural Science Foundation of China (No. 81170029).