MW‑9, a chalcones derivative bearing heterocyclic moieties, attenuates experimental autoimmune encephalomyelitis via suppressing pathogenic T17 cells.

Previous studies have indicated that MW‑9, a chalcones derivative bearing heterocyclic moieties, has considerable anti‑inflammatory activity . Whether MW‑9 may be used to treat inflammation‑based diseases, such as multiple sclerosis, remains unknown. The present study was designed to determine the effect and underlying mechanism of MW‑9 in experimental autoimmune encephalomyelitis (EAE). Female C57BL/6 mice immunized with MOG were treated with or without MW‑9, then the clinical scores and other relevant parameters were investigated. Production of cytokines and specific antibodies were monitored by ELISA assays. Surface marker, Treg cell, and intracellular cytokines (IL‑17A and IFN‑γ) were detected by flow cytometry, and mRNA expression in the helper‑T (T)17 cell‑related signaling pathway was examined by reverse transcription‑quantitative (RT‑q) PCR analysis. T17 cell differentiation assay was performed. Herein, the present results demonstrated that oral administration of MW‑9 reduced the severity of disease in EAE mice through slowing down infiltration process, inhibiting the demyelination, blocking anti‑MOG IgG antibody production (IgG, IgG and IgG), and decreasing accumulation of CD11bGr‑1 neutrophils from EAE mice. MW‑9 treatments also led to significantly decreased IL‑17A production and IL‑17 expression in CD4 T‑cells, but had no detectable influence on development of T1 and T‑regulatory cells . RT‑qPCR analysis showed that within the spinal cords of the mice, MW‑9 blocked transcriptional expression of TH17‑associated genes, including , , and . In T17 cell differentiation assay, MW‑9 inhibited differentiation of 'naïve' CD4 T‑cells into T17 cells and reduced the IL‑17A production. The data demonstrated that MW‑9 could attenuate EAE in part through suppressing the formation and activities of pathogenic T17 cells.