摘要

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 beta 1-Fc fusion protein (tIL12r beta 1/Fc) binding multiple forms of the p40 subunit of human IL-12 and IL-23. tIL12r beta 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 beta 1/Fc suppressed Th1 (IFN-gamma(+) alone) and IFN-gamma(+) IL-17(+) as well as the population of classic Th17 (IL-17(+) alone) cells in vivo. Furthermore, tIL12r beta 1/Fc ameliorated EAE at the peak of disease via the inhibition of STAT pathway, thereby causing a prominent reduction of ROR gamma t (Th17) and T-bet (Th1) expression. Notably, tIL12r beta 1/Fc could increase the relative number of CD4(+) Foxp3(+) regulatory T cells. These findings indicates that tIL12r beta 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.

  • 出版日期2015-10-6
  • 单位天然药物活性组分与药效国家重点实验室; 中国药科大学