IL-35 Is Involved in the Pathogenesis of Guillain-Barré Syndrome Through Its Influence on the Function of CD4+ T Cells

Immunol Invest. 2015;44(6):566-77. doi: 10.3109/08820139.2015.1043671.

Abstract

CD4+ T cells and many cytokines play critical roles in the pathogenesis of Guillain-Barré Syndrome (GBS), an immune-mediated inflammatory disease. However, the role of IL-35, a novel member of the IL-12 cytokine family, in this kind of disease has not yet been elucidated. In this study, we investigated the functional changes of CD4+ T cells from GBS patients with IL-35 treatment in vitro. This study involved 21 GBS patients and an equal number of healthy controls (HCs). The results indicated that the average concentration of IL-35 in the plasma of GBS patients was lower than that of healthy controls (HCs). Increased levels of STAT1, STAT3 and STAT4 proteins and T-bet, ROR γt, IFN-γ and IL-17A mRNA were observed in CD4+ T cells from GBS patients. In contrast, the levels of STAT5 and STAT6 proteins and GATA3, Foxp3, IL-4 and TGF-β1 mRNAs were decreased in GBS patients in comparison with those of HCs. In addition, treatment of CD4+ T cells from GBS patients with IL-35 upregulated IL-35, STAT5 and STAT6 protein and T-bet, GATA3, Foxp3, IFN-γ, IL-4, IL-17A and TGF-β1 mRNA while inhibited levels of STAT3 and STAT4 protein and RORγt and IL-17A mRNA. These results indicate that IL-35 might play a potential role in GBS pathogenesis. Further studies are required in order to evaluate its role in GBS.

Keywords: CD4+ T cells; Guillain–Barré Syndrome; IL-35; STAT; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • Cytokines / blood
  • Cytokines / immunology*
  • Female
  • Guillain-Barre Syndrome / blood
  • Guillain-Barre Syndrome / immunology*
  • Humans
  • Male
  • Middle Aged
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • RNA, Messenger / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Young Adult

Substances

  • Cytokines
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RNA, Messenger
  • Transcription Factors