title: A potential immunopathogenic role for reduced IL-35 expression in allergic asthma.
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.
authors.affiliation: a Department of Respiratory Medicine , Zhongnan Hospital of Wuhan University , Wuhan , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Yi-fei
authors.initials: YF
authors.lastname: Chen
authors.forename: Jiong
authors.initials: J
authors.lastname: Yang
mesh_terms: D000328:Adult; D001249:Asthma / Q000097:blood / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D021122:Protein Subunits / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016207:Cytokines; D021122:Protein Subunits; D012333:RNA, Messenger
keywords: Allergic asthma; CD4+CD25− T cells; IL-35; IL-4, proliferative responses