Journal Article
. 2006 Apr; 12(5):574-9.
doi: 10.1038/nm1385.

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

Je-Min Choi 1 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  
Affiliations
  • PMID: 16604087
  •     56 citations

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 (T(H)2) 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.

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