Small-molecule Cyclopeptide Roseotoxin B Ameliorates Contact Dermatitis In Mice Through Excessive Activation Of Autophagy In Activated T Lymphocytes

Allergic contact dermatitis(ACD)exhibits a delayed hypersensitivity,which is mainly caused by T cell.ACD with clinical symptoms including vesiculation,edema,and erythema,is usually treated with cyclosporine A(CsA)and glucocorticoids.These immunosuppressive agents can effectively regulate the body's immune overreaction,improve symptoms of diseases.However,mostly show poor selectivity,with some serious side-effects.There is still an urgent need for a potent agent against excessive activation of T cells and treating diseases as far as possible to avoid or reduce the drug side effects.Roseotoxin B,a natural cyclopeptide isolated from the fermentation products of Trichothecium roseum,shows a powerful anti-bacteria effective,meanwhile,the regulative effect has been indicatied.At the first part,we present a review on Allergic contact dermatitis and Roseotoxin B,incuding a brief introduction of Allergic contact dermatitis and the potential drug of Roseotoxin B for treatment of autoimmune disease.Next,an animal model of Allergic contact dermatitis induced by PC1 was established to study the effect of Roseotoxin B.The results showed that administration of Roseotoxin B can obviously improve the ear swelling degree and ear tissue lesionss of ACD model mice.At the cellular level,we explore the influence of Roseotoxin B to activated T cell.The results indicated that the influence of Roseotoxin B to activated T cell was expolred,and Roseotoxin B showed an ability to inhibit the T-cell proliferation,inflammatory cytokine releasing,and cell cycle arrest,without an effect on activation procession of T cells.All of these results mean that Roseotoxin B can ameliorate Allergic contact dermatitis,on animal mode and cellular level.At the third part,we explored the mechanism underlines the contact hypersensitivity effect of Roseotoxin B.Whith results,Roseotoxin B could inhibit T-cell proliferation and the pro inflammatory cytokines production,cause cell cycle arrest in ConA-activated T cells,through excessive activation of autophagy in activated T lymphocytes.In vivo experiments reveal that the curative effect of Roseotoxin B to ACD was dependent on autophagy mediated by LC3 gene.In summary,we confirm the effect of Roseotoxin B on Allergic contact dermatitis,then we find out the mechanism behind it,proliferation of T lymphocytes are inhibited through upregulating level of autophagy.Our research not only provides the example of through regulating autophagy improve T cell-mediated immune response,but also offers a new potential drug for Allergic contact dermatitis.