Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation

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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120 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)574-579
Number of pages6
JournalNature Medicine
Issue number5
Publication statusPublished - 2006 May

Bibliographical note

Funding Information:
We thank A. Bothwell and T. Morio for the comments on the manuscript and all members of Immune Cell Engineering Laboratory, Department of Biotechnology, Yonsei University for their spiritual help. This work was supported in part by research grants to S.K.L. from Korea Institute of Industrial Technology Evaluation and Planning (M1-0310-40-0000), Korea Health Industry Development Institute (0412-DB00-0101-0011), Korea Science and Engineering Foundation (2005-00117) and Korea Rural Economic Institute (204081-3). This work was also supported in part by research grants to C.S.P. from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (01-PJ3-PG6-01GN04-003).

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


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