Urolithin A ameliorates experimental autoimmune encephalomyelitis by targeting aryl hydrocarbon receptor
Pei-Xin Shen, Xing Li, Si-Ying Deng, Li Zhao, Yanyan Zhang, Xin Deng, Bing Han, Jie Yu, Yin Li, Zhezhi Wang, Yuan Zhang
Abstract
BACKGROUND: Urolithin A (URA) is an intestinal microbiota metabolic product from ellagitannin-containing foods with multiple biological activities. However, its role in autoimmune diseases is largely unknown. Here, for first time, we demonstrate the therapeutic effect of URA in an experimental autoimmune encephalomyelitis (EAE) animal model. METHODS: Therapeutic effect was evaluated via an active and passive EAE animal model in vivo. The function of URA on bone marrow-derived dendritic cells (BM-DCs), T cells, and microglia were tested in vitro. FINDINGS: T cell co-culture system. Moreover, we confirmed URA inhibited pathogenicity of Th17 cells in adoptive EAE. Mechanism of URA action was directly targeting Aryl Hydrocarbon Receptor (AhR) and modulating the signaling pathways. INTERPRETATION: Collectively, our study offers new evidence that URA, as a human microbial metabolite, is valuable to use as a prospective therapeutic candidate for autoimmune diseases.