Ponesimod modulates the Th1/Th17/Treg cell balance and ameliorates disease in experimental autoimmune encephalomyelitis

J Neuroimmunol. 2021 Jul 15:356:577583. doi: 10.1016/j.jneuroim.2021.577583. Epub 2021 Apr 23.

Abstract

Sphingosine-1-phosphate receptor 1 (S1P1) plays an important role in autoimmune disease. Here, we evaluated whether ponesimod, an S1P1 modulator, affects inflammation in experimental autoimmune encephalomyelitis (EAE) and investigated Th1/Th2/Th17/Treg cell subsets. Ponesimod treatment ameliorated EAE and alleviated inflammatory infiltration. Compared with untreated EAE, ponesimod-treated mice had lower Th1 and Th17 cell numbers and higher Treg cell numbers; their IFN-γ, T-bet, IL-17, and RORγt levels as well as their pmTOR/mTOR ratio were diminished, while their TGF-β and Foxp3 levels were enhanced. These results suggest that ponesimod modulates the Th1/Th17/Treg balance and regulates the mTOR pathway.

Keywords: Experimental autoimmune encephalomyelitis; Multiple sclerosis; Ponesimod; Sphingosine-1-phosphate receptor; Th1; Th17; Treg.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Female
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / immunology
  • Mice
  • Mice, Inbred C57BL
  • Sphingosine 1 Phosphate Receptor Modulators / pharmacology
  • Sphingosine 1 Phosphate Receptor Modulators / therapeutic use
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use*

Substances

  • Inflammation Mediators
  • Sphingosine 1 Phosphate Receptor Modulators
  • Thiazoles
  • ponesimod