Effect And Mechanism Of Lidocaine Promotion On The Differentiation Of Regulatory T Cells In Atopic Dermatitis

Objective: We sought to address the regulation of Treg cells and other key cytokines in both AD patients and murine AD models to explore the immunomodulatory effect of lidocaine. The mechanism was explored with in vitro Treg differentiation from Naive CD4+ T cells, of which the further specific signaling pathway was defined.Methods: The percentages of Treg cells in PBMCs from 20 AD patients were measured with flow cytometry. The key transcriptional factor Fox P3 m RNA expression and other key cytokines involved in AD, such as IFN-γ, IL-4, IL-17 A, IL-17 E m RNA expression were dected by means of RT-PCR. OVAsensitized murine AD models were established to assess the effect of lidocaine. The pecentages of Treg cells in murine dermis of lesional skin, spleen and lymph nodes were detected with flow cyometry. Fox P3, IFN-γ,IL-4, IL-17 A, IL-17 E m RNA expression in the lesional skins were also measured. We also induced differentiation in vitro to clarify the effect of lidocaine on modulation of Treg cells. The activation of TGF-β/Smad3 and NF-кB signaling pathways were also explored with Western-Blot analysis to define its specific signaling pathway.Results: Lidocaine therapy can enhance the percentage of Treg cells and promoted Fox P3 m RNA expression in both PBMCs of AD patients and lesional skins of murine AD models. Lidocaine therapy also ameliorate Th1/Th2 and IL-17A/IL-17 E imbalance to different extent in both AD patients and murine AD models. Lidocaine promoted Fox P3 transcription specificly by activation of TGF-β-induced Smad3 phosphorylation, but not with activation of NF-кB signaling pathway.Conclusion: The study sheds new light on the critical role and underlying the mechanism of lidocaine in the regulation of Treg cells, which provides a novel rationale for lidocaine therapy for AD inflammation.