A novel human truncated IL12r?1-Fc fusion protein ameliorates experimental autoimmune encephalomyelitis via specific binding of p40 to inhibit Th1 and Th17 cell differentiation.

ABSTRACT: Interleukin (IL)-12 and IL-23 respectively driving polarization of T helper (Th) 1 and Th17 cells has been strongly implicated in the pathogenesis of both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). In this study, we first constructed, expressed and purified a novel human truncated IL12r?1-Fc fusion protein (tIL12r?1/Fc) binding multiple forms of the p40 subunit of human IL-12 and IL-23. tIL12r?1/Fc was found to effectively ameliorate MOG35-55-induced EAE through reducing the production of Th1- and Th17-polarized pro-inflammatory cytokines and suppressing inflammation and demyelination in the focused parts. Moreover, tIL12r?1/Fc suppressed Th1 (IFN-?(+) alone) and IFN-?(+) IL-17(+) as well as the population of classic Th17 (IL-17(+) alone) cells in vivo. Furthermore, tIL12r?1/Fc ameliorated EAE at the peak of disease via the inhibition of STAT pathway, thereby causing a prominent reduction of ROR?t (Th17) and T-bet (Th1) expression. Notably, tIL12r?1/Fc could increase the relative number of CD4(+) Foxp3(+) regulatory T cells. These findings indicates that tIL12r?1/Fc is a novel fusion protein for specific binding multiple forms of p40 subunit to exert potent anti-inflammatory effects and provides a valuable approach for the treatment of MS and other autoimmune diseases.

SUBMITTER: Guo W 

PROVIDER: S-EPMC4745676 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature