Teriflunomide suppresses T helper cells and dendritic cells to alleviate experimental autoimmune uveitis

Biochem Pharmacol. 2019 Dec:170:113645. doi: 10.1016/j.bcp.2019.113645. Epub 2019 Sep 20.

Abstract

Autoimmune uveitis (AU), a sight-threatening intraocular disorder, is still a challenge for ophthalmologists in clinic. Teriflunomide has been approved for multiple sclerosis (MS) in 2012 for its immunoregulatory function. However, the effect and mechanisms of teriflunomide in uveitis are still unknown. In this investigation, we used a murine model of non-infectious uveitis, experimental autoimmune uveitis (EAU), to explore the anti-inflammatory features of teriflunomide. Treatment with teriflunomide resulted in reduced clinical and pathological scores of retinal inflammations, accompanied by decreased intraocular infiltration of Th17 and Th1 cells in EAU mice. Meanwhile, teriflunomide treatment inhibited the proliferation and polarization of CD4+ T cells to Th17 and Th1 cells. Moreover, adoptive transfer of teriflunomide primed IRBP1-20-T cells failed to induce EAU. Interestingly, we found that teriflunomide suppressed the maturation and function of dendritic cells (DCs) both in vivo and in vitro. In conclusion, our findings suggest that teriflunomide alleviates inflammation in EAU mice by down-regulating Th17 and Th1 cells and suppresses the maturation and function of DCs for the first time.

Keywords: Autoimmune uveitis; CD4+ T cells; Dendritic cells maturation; Experimental autoimmune uveitis; Teriflunomide; Teriflunomide (PubChem CID: 54684141).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coculture Techniques
  • Crotonates / pharmacology
  • Crotonates / therapeutic use*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Eye Proteins / toxicity
  • Female
  • Hydroxybutyrates
  • Mice
  • Mice, Inbred C57BL
  • Nitriles
  • Retinol-Binding Proteins / toxicity
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*
  • Toluidines / pharmacology
  • Toluidines / therapeutic use*
  • Uveitis / chemically induced
  • Uveitis / drug therapy*
  • Uveitis / immunology*

Substances

  • Crotonates
  • Eye Proteins
  • Hydroxybutyrates
  • Nitriles
  • Retinol-Binding Proteins
  • Toluidines
  • interstitial retinol-binding protein
  • teriflunomide