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Teriflunomide suppresses T helper cells and dendritic cells to alleviate experimental autoimmune uveitis.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 2019 Dec; Vol. 170, pp. 113645. Date of Electronic Publication: 2019 Sep 20. - Publication Year :
- 2019
-
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 IRBP <subscript>1-20</subscript> -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.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Coculture Techniques
Crotonates pharmacology
Dendritic Cells drug effects
Disease Models, Animal
Eye Proteins toxicity
Female
Hydroxybutyrates
Mice
Mice, Inbred C57BL
Nitriles
Retinol-Binding Proteins toxicity
Th1 Cells drug effects
Th17 Cells drug effects
Toluidines pharmacology
Uveitis chemically induced
Crotonates therapeutic use
Dendritic Cells immunology
Th1 Cells immunology
Th17 Cells immunology
Toluidines therapeutic use
Uveitis drug therapy
Uveitis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2968
- Volume :
- 170
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 31545975
- Full Text :
- https://doi.org/10.1016/j.bcp.2019.113645