Premium
Mitigated Tregs and Augmented Th17 Cells and Cytokines are Associated with Severity of Experimental Autoimmune Neuritis
Author(s) -
Wang X.,
Zheng X.Y.,
Ma C.,
Wang X.K.,
Wu J.,
Adem A.,
Zhu J.,
Zhang H.L.
Publication year - 2014
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12201
Subject(s) - pathogenesis , immunology , foxp3 , medicine , neuritis , peripheral blood mononuclear cell , immune system , cytokine , interleukin 17 , autoimmune disease , biology , antibody , in vitro , biochemistry , psychiatry
Experimental autoimmune neuritis ( EAN ), an animal model of human Guillain–Barré syndrome, has long been considered as a T helper (Th) 1 cell–mediated autoimmune disorder. However, deficiency of IFN ‐ γ , a signature Th1 cytokine, aggravated EAN , with features of elevated production of IL ‐17A, despite an alleviated systemic Th1 immune response. We hypothesized that Th17 cells and their cytokines might play a pathogenic role in EAN . To further clarify the roles of these Th and regulatory T cell (Treg) cytokines in the pathogenesis of EAN and their interrelationship, we investigated the expression of Th1/Th2/Th17/Treg cytokines in EAN in this study. We found that the levels of Th17 cells and IL ‐17A in cauda equina ( CE )‐infiltrating cells and splenic mononuclear cells ( MNC s) as well as in serum paralleled the disease evolution, which increased progressively during the initiation stage and reached higher value at the peak of EAN . The same pattern was also noticed for the expression of IL ‐22. The diverse expression profiles of FoxP3, IL ‐17 receptors A and C were seen in CE ‐infiltrating cells and splenic MNC s in EAN . These findings indicate a major pro‐inflammatory role of Th17 cells and IL ‐17A in the pathogenesis of EAN . Therapeutic interventions may be focused upon inhibiting Th17 cells and their cytokines in the early phase of EAN , so as to delay and suppress clinical signs of the disease, which has relevance for future studies on pathogenesis and treatment of GBS in humans.