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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 <jats:italic>\u03b1<\/jats:italic>\u2010helical configurational melittin (<jats:italic>\u03b1<\/jats:italic>\u2010melittin\u2010NP) is developed to overcome T cell\u2010mediated inflammatory reactions in an oxazolone (OXA)\u2010induced contact hypersensitivity mouse model and OXA\u2010induced AD\u2010like mouse model. Intradermal injection of low\u2010dose <jats:italic>\u03b1<\/jats:italic>\u2010melittin\u2010NPs prevents the skin damage caused by melittin administration alone and efficiently targeted lymph nodes. Importantly, melittin and <jats:italic>\u03b1<\/jats:italic>\u2010melittin\u2010NPs restrain RelB activity in dendritic cells (DCs) and further suppresses dendritic cell activation and maturation in lymph nodes. Furthermore, low\u2010dose <jats:italic>\u03b1<\/jats:italic>\u2010melittin\u2010NPs leads to relief of antigen recognition\u2010induced effector T cell arrest in the dermis and inhibited allergen\u2010specific T cell proliferation and activation. Significantly, this approach successfully controls Th1\u2010type cytokine release in the ACD model and restricts Th2\u2010type cytokine and IgE release in the AD\u2010like model. Overall, intradermal delivery of low\u2010dose <jats:italic>\u03b1<\/jats:italic>\u2010melittin\u2010NPs efficiently elicits immunosuppression against T cell\u2010mediated immune reactions, providing a promising therapeutic strategy for treating skin disorders not restricted to the lesion region.<\/jats:p>","DOI":"10.1002\/advs.202204184","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T15:29:00Z","timestamp":1673623740000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Melittin\u2010Carrying Nanoparticle Suppress T Cell\u2010Driven Immunity in a Murine Allergic Dermatitis Model"],"prefix":"10.1002","volume":"10","author":[{"given":"Zheng","family":"Liu","sequence":"first","affiliation":[{"name":"Britton Chance Center and MOE Key Laboratory for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology  Wuhan Hubei 430074 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