Author: ["Je-Min Choi","Mi-Hyun Ahn","Wook-Jin Chae","Yung-Gook Jung","Jae-Chul Park","Hyun-Mi Song","Young-Eun Kim","Jung-Ah Shin","Choon-Sik Park","Jung-Won Park","Tae-Kwann Park","Jung-Hoon Lee","Byung-Fhy Seo","Kyun-Do Kim","Eun-Sung Kim","Dong-Ho Lee","Seung-Kyou Lee","Sang-Kyou Lee"]
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Abstract
CTLA-4 is a negative regulator of T-cell activation, and its inhibitory effects can be accomplished either by competition with CD28 or by transmitting negative signals through its intracellular domain. To utilize the cytoplasmic domain of CTLA-4 to suppress allergic inflammation, we fused it to a novel protein-transduction domain in the human transcriptional factor Hph-1. Transduction efficiency was verified in vitro and in vivo after ocular, intranasal and intradermal administration. After transduction into T cells, the Hph-1–ctCTLA-4 fusion protein inhibited the production of interleukin (IL)-2, and downregulated CD69 and CD25. Intranasal administration of Hph-1–ctCTLA-4 resulted in markedly reduced infiltration of inflammatory cells, secretion of T helper type 2 (TH2) cytokines, serum IgE levels and airway hyper-responsiveness in a mouse model of allergic airway inflammation. These results indicated that Hph-1–ctCTLA-4 constitutes an effective immunosuppressive protein drug for potential use in the treatment of allergic asthma, via nasal administration.Cite this article
Choi, JM., Ahn, MH., Chae, WJ. et al. Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation. Nat Med 12, 574–579 (2006). https://doi.org/10.1038/nm1385 