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

Authors
 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 
Citation
 NATURE MEDICINE, Vol.12(5) : 574-579, 2006 
Journal Title
 NATURE MEDICINE 
ISSN
 1078-8956 
Issue Date
2006
MeSH
Administration, Intranasal* ; Animals ; Antigens, CD ; Antigens, Differentiation/administration & dosage* ; Antigens, Differentiation/genetics ; Antigens, Differentiation/immunology* ; Asthma*/immunology ; Asthma*/prevention & control ; Bronchial Hyperreactivity ; CTLA-4 Antigen ; Carrier Proteins/genetics ; Carrier Proteins/metabolism* ; Female ; Humans ; Immunoconjugates/administration & dosage ; Immunoconjugates/genetics ; Immunoconjugates/immunology ; Immunosuppressive Agents*/administration & dosage ; Immunosuppressive Agents*/immunology ; Inflammation*/immunology ; Inflammation*/prevention & control ; Male ; Mice ; Mice, Inbred BALB C ; Ovalbumin/immunology ; Polycomb Repressive Complex 1 ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/administration & dosage ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/immunology ; Transduction, Genetic
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.
Full Text
http://www.nature.com/nm/journal/v12/n5/full/nm1385.html
DOI
10.1038/nm1385
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Park, Jung Won(박중원) ORCID logo https://orcid.org/0000-0003-0249-8749
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/109668
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