Abstract
Allergic contact dermatitis (ACD) and atopic dermatitis (AD) are the most common human skin disorders. Although corticosteroids have been widely used to treat ACD and AD, the side effects of corticosteroids encourage researchers to explore new immunoregulatory treatments. Here, an immunomodulatory approach based on lipid nanoparticles carrying α-helical configurational melittin (α-melittin-NP) is developed to overcome T cell-mediated inflammatory reactions in an oxazolone (OXA)-induced contact hypersensitivity mouse model and OXA-induced AD-like mouse model. Intradermal injection of low-dose α-melittin-NPs prevents the skin damage caused by melittin administration alone and efficiently targeted lymph nodes. Importantly, melittin and α-melittin-NPs restrain RelB activity in dendritic cells (DCs) and further suppresses dendritic cell activation and maturation in lymph nodes. Furthermore, low-dose α-melittin-NPs leads to relief of antigen recognition-induced effector T cell arrest in the dermis and inhibited allergen-specific T cell proliferation and activation. Significantly, this approach successfully controls Th1-type cytokine release in the ACD model and restricts Th2-type cytokine and IgE release in the AD-like model. Overall, intradermal delivery of low-dose α-melittin-NPs efficiently elicits immunosuppression against T cell-mediated immune reactions, providing a promising therapeutic strategy for treating skin disorders not restricted to the lesion region.