Abstract
Background: Mesenchymal stem cells (MSCs) has therapeutic potential for Atopic dermatitis (AD) due to their immunoregulatory effects. However, the underlying mechanisms for therapeutic efficacy of ADSCs on AD is still unclear. Objectives: We sought to investigate the therapeutic effect and mechanisms of adipose-derived stem cells (ADSCs) on AD using an ovalbumin-induced AD mouse model. Methods: AD mice were treated with mice-derived ADSCs, cortisone, or PBS. The therapeutic effect was determined via gross examination and additional in vitro assays using skin samples and blood. To further explore the underlying mechanisms, RNA sequencing analyses and co-culture assays were conducted.Results: ADSCs treatment attenuated the symptoms associated with AD, decreased the serum IgE level and mast cells infiltration. Tissue levels of T-cell relevant pro-inflammatory cytokine production, including IL-4R and IL-17A, were suppressed in both ADSCs and cortisone treatment groups. Genomics and bioinformatics analyses demonstrated a significant enrichment of certain of inflammation related pathway in the down regulated genes after the application of ADSCs and cortisone, specifically the IL-17 signaling pathway. Co-culture experiments revealed that ADSCs significantly suppressed the expression of pro-inflammation cytokines IL-17A and RORγT, as well as the proliferation of Th17 cells. Moreover, the expression of PD-L1, TGF-β, PGE2 was significantly upregulated in the co-cultured ADSCs compare to monocultured ADSCs. Conclusion: Taken together, our data may demonstrate that ADSCs ameliorate OVA- induced AD in mice by down-regulating IL-17 secretion of Th17 cells.
Korean Red Ginseng improves atopic dermatitis-like skin lesions by suppressing expression of proinflammatory cytokines and chemokines in vivo and in vitro
