The Small-Molecule compound baicalein alleviates experimental autoimmune encephalomyelitis by suppressing pathogenetic CXCR6+ CD4 cells

Abstract

CXC chemokine receptor6 (CXCR6)-based immunotherapy plays a significant role in autoimmune diseases, however, little is known about possible small compounds that inhibit pathogenic CXCR6⁺ T cells for treating multiple sclerosis (MS). Baicalein, a flavonoid isolated from Scutellarin baicalensis (Huang Qin), was shown to exert therapeutic effects on MS, but the underlying mechanisms are largely unknown. In the current study, we found that baicalein inhibited Th1 and Th17 differentiation in vitro. Oral administration of baicalein (25 mg/kg) significantly reduced the disease severity and the infiltration process, decreased the extent of demyelination in EAE, and selectively blocked IL-17A production and specific antibodies (IgG and IgG₃) in MOG_35-55-induced specific immune responses. In addition, the expression of CD4 cell effectors (CD44^hiCD62L^low) and pathogenic Th17 cells was decreased by baicalein treatment. Furthermore, baicalein treatment largely decreased CXCR6⁺ CD4 and CD8 cells and prominently inhibited CXCR6⁺ Th17 cells in EAE. Taken together, the findings of this study suggest for the first time that baicalein may ameliorate EAE by suppressing pathogenetic CXCR6⁺ CD4 cells.

Keywords: Baicalein; CXCR6; Experimental Autoimmune Encephalomyelitis; Multiple Sclerosis; Th17 cells.