Metformin Attenuates Atopic Dermatitis by Inhibiting CD40 Expression in CD11c+DC via the mTOR Pathway

Atopic dermatitis (AD), a common chronic inflammatory skin disease, can be caused by various cues. People with type 2 diabetes (T2D) tend to have a higher risk of getting atopic dermatitis (AD). The agent that can cure both AD and T2D has aroused general concern. In the present study, we investigated if hypoglycemic agents, metformin prevents chronic allergic reactions via the generation of CD40, which plays a preventive role in the pathogenesis of allergic disease. Frist, in vitro cell stimulation experiment, orally administered metformin reduced inflammatory T cell response and the expression levels of CD40 and other mTOR-regulated proteins, p70S6K1 and 4E-BP1. Metformin treatment enhanced the induction of CD40 from CD11c + DC, probably via the inhibition of mTOR activation and the following down-regulated p70S6K1 and 4E-BP1 according to the results of flow cytometry, western blot and RT-PCR analysis. Afterwards, CD40 in CD11c + DC was deleted by transfection with si-RNA, which did not impair expression of mTOR, suggesting that CD40 is downstream of mTOR and has no negative feedback to mTOR. Together, data shown in our study provide evidences that metformin may have potential to be an orally effective immunosupperssor to chronic inflammatory diseases.