4.3 Article

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

Journal

JOURNAL OF NEUROIMMUNOLOGY
Volume 356, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.jneuroim.2021.577583

Keywords

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

Funding

  1. National Natural Science Foundation of China [81701186]
  2. key project of Medical Science Research in Hebei Province [20200868]

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Ponesimod treatment improved EAE and reduced inflammatory infiltration, decreasing Th1 and Th17 cell numbers while increasing Treg cell numbers, and modulated the levels of related cytokines and signaling pathways.
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-gamma, T-bet, IL-17, and ROR gamma t levels as well as their pmTOR/mTOR ratio were diminished, while their TGF-beta and Foxp3 levels were enhanced. These results suggest that ponesimod modulates the Th1/Th17/Treg balance and regulates the mTOR pathway.

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