Decreased Circulating Interleukin-35 Levels Are Related to Interleukin-4-Producing CD8+ T Cells in Patients with Allergic Asthma

Interleukin (IL)-35 is a newly discovered suppressive cytokine and has been shown to alleviate  inflammatory  and  autoimmune  diseases.  The  purpose  of  this  study  was  to investigate immunomodulatory capacity of IL-35 in patients with allergic asthma.IL-35 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) were detected  by  quantitative  real-time  PCR  (qPCR).  The  frequencies  of  cytotoxic  T  cells (Tc)1,Tc2  and  Tc17  cells  were  measured  by  flow  cytometry.  Plasma  levels  of  IL-35, interferon (IFN)-γ, IL-4, and IL-17 were examined by enzyme-linked immunosorbent assay (ELISA). The correlations between plasma IL-35 levels and Tc1, Tc2, and Tc17 cytokine production in allergic asthmatics (n = 25) and healthy controls (n = 12) were analyzed by Pearson’s test.IL-35 protein and mRNA expression levels were down-regulated in allergic asthmatics compared with healthy controls. The frequencies of Tc2 and Tc17 cells were significantly increased in patients with asthma, and the frequency of Tc1 cells did not differ between asthmatic patients and healthy controls. Similarly, plasma levels of IL-4 and IL-17 were significantly increased in asthmatic patients, while there was no difference in IFN-γ levels between allergic asthma patients  and  healthy  controls.  More importantly,  plasma  IL-35 protein levels were negatively correlated with the frequency of IL-4-producing CD8+ T (Tc2) cells and with the IL-4 level in patients with allergic asthma.Our results suggest that decreased circulating IL-35 levels could contribute to the pathogenesis of allergic asthma by regulating CD8+ T cells.