Sesamin Induces MCL-1-Dependent Apoptosis in Activated T Cells and Ameliorates Experimental Atopic Dermatitis.

Sesamin, a natural lignan derived from , has been reported to possess anti-inflammatory and pro-apoptotic properties. However, its effect on T cell-mediated diseases and the underlying molecular mechanisms remain unclear. In this study, we demonstrate that sesamin selectively induces apoptosis in activated T cells through direct interaction with MCL-1, a critical anti-apoptotic protein of the Bcl-2 family. Sesamin suppressed IL-2 expression, CD69 upregulation, and proliferation in activated human and murine T cells. Molecular docking predicted strong binding of sesamin to the BH3-binding groove of MCL-1, which was validated by pull-down and co-immunoprecipitation assays. Sesamin inhibited MCL-1 phosphorylation at Ser64 and disrupted its heterodimerization with Bak, promoting caspase-3/8 cleavage and apoptotic death selectively in activated, but not resting, T cells. In a murine model of atopic dermatitis, oral administration of sesamin ameliorated pathological skin symptoms, reduced Th2/Th17 cytokine expression, serum IgE, mast cell infiltration, and lymph node hypertrophy. These effects correlated with suppressed MCL-1 activity and enhanced apoptosis in inflamed tissue. Our findings suggest that sesamin modulates immune responses via a novel MCL-1-dependent mechanism and represents a promising dietary-derived therapeutic strategy for T cell-driven chronic inflammatory diseases.