A potential immunopathogenic role for reduced IL-35 expression in allergic asthma

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-gamma 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.