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Apremilast Regulates the Teff/Treg Balance to Ameliorate Uveitis via PI3K/AKT/FoxO1 Signaling Pathway

Autoimmune uveitis (AU), being one of the sight-threatening ocular inflammatory disorders, has been widely regarded by ophthalmologists and immunologists as a great challenge. Apremilast, a phosphodiesterase-4 inhibitor (PDE4i), which was approved by the U.S. Food and Drug Administration (FDA) for t...

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Detalles Bibliográficos
Autores principales: Chen, Yuxi, Li, Zhuang, Li, He, Su, Wenru, Xie, Yanyan, Pan, Yuan, Chen, Xiaoqing, Liang, Dan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705241/
https://www.ncbi.nlm.nih.gov/pubmed/33281814
http://dx.doi.org/10.3389/fimmu.2020.581673
Descripción
Sumario:Autoimmune uveitis (AU), being one of the sight-threatening ocular inflammatory disorders, has been widely regarded by ophthalmologists and immunologists as a great challenge. Apremilast, a phosphodiesterase-4 inhibitor (PDE4i), which was approved by the U.S. Food and Drug Administration (FDA) for the treatment of active psoriatic arthritis in 2014, has been attracting researchers, who are exploring its efficiency and mechanism on uveitis. In this study, we used an experimental autoimmune uveitis (EAU), a representative model for human AU, to investigate the effect of apremilast on regulating anti-inflammatory mediators. Our study demonstrated that apremilast treatment resulted in a decrease in vascular leakage, macular edema, and inflammatory cell infiltration in the retina, corresponding to decreased clinical and pathological scores. Specifically, apremilast decreased the proportion and population of Th17 cells and increased the proportion and population of T regulatory (Treg) cells. Mechanistically, apremilast may regulate Th17 and Treg cells by inhibiting the phosphorylation of the phosphoinositide 3-kinase (PI3K)/protein kinase B(AKT)/Forkhead box O1 (FoxO1) signaling pathway. These findings suggested that apremilast alleviated EAU by regulating Th17 and Treg through the PI3K/AKT/FoxO1 pathway.