IFN-α and vitamin B6-induced galectin-9 promotes the immunomodulatory function of human clonal mesenchymal stem cells

초록

Background Mesenchymal stem cells (MSCs) possess a variety of immunomodulatory functions that can vary depending on the MSC line. Investigating priming strategies is essential for increasing the immunomodulatory potential of MSCs. Methods Human clonal MSCs (cMSCs) were primed with TNF-alpha, IFN-gamma, IL-1 beta, IFN-alpha, and vitamin B6. Their immunomodulatory functions, including T-cell proliferation and cytokine production, were analyzed. The primed cMSCs were injected intravenously into a mouse model of ovalbumin-induced atopic dermatitis (AD), and their therapeutic effects were evaluated. Results We identified IFN-alpha and vitamin B6 as promising priming agents when they are combined with TNF-alpha and IFN-gamma. The primed cMSCs showed expression of galectin-9 (Gal-9), IL-1Ra, and PDL-1. Gal-9 facilitates the induction of regulatory T cells (Tregs) and apoptosis. Treatment with primed cMSCs significantly alleviated pathological changes in an AD mouse model. Notable improvements included a reduction in epidermal thickness (p < 0.05), a decreased number of mast cells and eosinophils in the dermis (p < 0.01), restored expression of claudin-1 in the epidermis (p < 0.0001), and lower serum levels of IgE (p < 0.05). Conclusions This novel combination of priming factors significantly promotes the immunomodulatory functions of cMSCs by inducing Gal-9. Consequently, Gal-9 may serve as an excellent biomarker for screening primed cMSCs for their immunomodulatory capabilities, facilitating a more accurate assessment of their therapeutic effectiveness.

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