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, Jungwon 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

Research output: Contribution to journalArticle

99 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)574-579
Number of pages6
JournalNature Medicine
Volume12
Issue number5
DOIs
Publication statusPublished - 2006 May 1

Fingerprint

Intranasal Administration
T-cells
Inflammation
Respiratory Hypersensitivity
T-Lymphocytes
Th2 Cells
Proteins
Immunosuppressive Agents
Human engineering
Infiltration
Immunoglobulin E
Interleukin-2
Fusion reactions
Down-Regulation
Asthma
Chemical activation
Cytokines
Serum
Pharmaceutical Preparations
Protein Domains

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Choi, Je Min ; Ahn, Mi Hyun ; Chae, Wook Jin ; Jung, Yung Gook ; Park, Jae Chul ; Song, Hyun Mi ; Kim, Young Eun ; Shin, Jung Ah ; Park, Choon Sik ; Park, Jungwon ; Park, Tae Kwann ; Lee, Jung Hoon ; Seo, Byung Fhy ; Kim, Kyun Do ; Kim, Eun Sung ; Lee, Dong Ho ; Lee, Seung Kyou ; Lee, Sang Kyou. / Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation. In: Nature Medicine. 2006 ; Vol. 12, No. 5. pp. 574-579.
@article{723d23e2c5fd4be6881dd5033a631b74,
title = "Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation",
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.",
author = "Choi, {Je Min} and Ahn, {Mi Hyun} and Chae, {Wook Jin} and Jung, {Yung Gook} and Park, {Jae Chul} and Song, {Hyun Mi} and Kim, {Young Eun} and Shin, {Jung Ah} and Park, {Choon Sik} and Jungwon Park and Park, {Tae Kwann} and Lee, {Jung Hoon} and Seo, {Byung Fhy} and Kim, {Kyun Do} and Kim, {Eun Sung} and Lee, {Dong Ho} and Lee, {Seung Kyou} and Lee, {Sang Kyou}",
year = "2006",
month = "5",
day = "1",
doi = "10.1038/nm1385",
language = "English",
volume = "12",
pages = "574--579",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "5",

}

Choi, JM, Ahn, MH, Chae, WJ, Jung, YG, Park, JC, Song, HM, Kim, YE, Shin, JA, Park, CS, Park, J, Park, TK, Lee, JH, Seo, BF, Kim, KD, Kim, ES, Lee, DH, Lee, SK & Lee, SK 2006, 'Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation', Nature Medicine, vol. 12, no. 5, pp. 574-579. https://doi.org/10.1038/nm1385

Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation. / Choi, Je Min; Ahn, Mi Hyun; Chae, Wook Jin; Jung, Yung Gook; Park, Jae Chul; Song, Hyun Mi; Kim, Young Eun; Shin, Jung Ah; Park, Choon Sik; Park, Jungwon; Park, Tae Kwann; Lee, Jung Hoon; Seo, Byung Fhy; Kim, Kyun Do; Kim, Eun Sung; Lee, Dong Ho; Lee, Seung Kyou; Lee, Sang Kyou.

In: Nature Medicine, Vol. 12, No. 5, 01.05.2006, p. 574-579.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation

AU - Choi, Je Min

AU - Ahn, Mi Hyun

AU - Chae, Wook Jin

AU - Jung, Yung Gook

AU - Park, Jae Chul

AU - Song, Hyun Mi

AU - Kim, Young Eun

AU - Shin, Jung Ah

AU - Park, Choon Sik

AU - Park, Jungwon

AU - Park, Tae Kwann

AU - Lee, Jung Hoon

AU - Seo, Byung Fhy

AU - Kim, Kyun Do

AU - Kim, Eun Sung

AU - Lee, Dong Ho

AU - Lee, Seung Kyou

AU - Lee, Sang Kyou

PY - 2006/5/1

Y1 - 2006/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33646587029&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646587029&partnerID=8YFLogxK

U2 - 10.1038/nm1385

DO - 10.1038/nm1385

M3 - Article

C2 - 16604087

AN - SCOPUS:33646587029

VL - 12

SP - 574

EP - 579

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 5

ER -