ID | 105964 |
Title Alternative | CCR4陽性細胞の選択的減少は、アレルギー性気道炎症を抑制する
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Author |
Honjo, Akifumi
Department of Respiratory Medicine & Rheumatology, Institute of Health Biosciences, The University of Tokushima Graduate School
Ogawa, Hirohisa
The University of Tokushima
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Sone, Saburo
The University of Tokushima
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Biragyn, Arya
National Institute on Aging
Nishioka, Yasuhiko
The University of Tokushima
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Keywords | CCR4
TARC-PE38
allergic inflammation
airway hyperresponsiveness
bronchial asthma
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Content Type |
Thesis or Dissertation
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Description | Back ground: Bronchial asthma is characterized by allergic airway inflammation involving C-C chemokine receptor type 4 (CCR4)-positive Th2 cells. As such, we hypothesize that the disease can be alleviated by targeted-elimination of CCR4+ cells. Thymus and activation-regulated chemokine (TARC)-PE38, a TARC fused the exotoxin fragment PE38 from Pseudomonas aeruginosa, has been shown to efficiently kill CCR4+ cells by delivering the exotoxin fragment PE38into CCR4+ cells. To test our hypothesis, we examined whether TARC-PE38could suppress allergic airway inflammation in a mouse model of house dust mite (HDM)-induced allergic airway inflammation.
Methods: We evaluated the effect of TARC-PE38 on the major characteristics of HDM-induced allergic airway inflammation. Airway hyper responsiveness, lung histopathology, lung Th1/Th2 cell populations, and concentrations of Th1/Th2 cytokines in the lungs were assessed in HDM-sensitized and challenged mice in the presence and absence of TARC-PE38. Results: TARC-PE38 efficiently suppressed allergic airway inflammation by significantly reducing airway hyperresponsiveness, the overall area of inflammation, and goblet cell hyperplasia. In HDM-sensitized and challenged mice, TARC-PE38 specifically reduced the numbers of CCR4+ cells. This reduction was associated with a significant decrease in the production of Th2 cytokines in the airway, and a decrease in the number of leukocytes, including macrophages, eosinophils and lymphocytes, within the subepithelial area of the lungs and airway lumen.TARC-PE38 had no effect on Th1 cells. Conclusion: Our data suggest that the elimination of CCR4+ cells viaTARC-PE38 treatment is sufficient to control allergic airway inflammation and airway hyperresponsiveness. |
Journal Title |
Respiratory Investigation
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ISSN | 22125345
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NCID | AA12579673
AA12797947
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Publisher | The Japanese Respiratory Society|Elsevier
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Volume | 51
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Issue | 4
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Start Page | 241
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End Page | 249
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Published Date | 2013-06-22
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Remark | 内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201312091001.pdf 論文本文 : LID201405271002.pdf 本論文は, 著者Akifumi Honjoの学位論文として提出され, 学位審査・授与の対象となっている。 |
EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第2653号
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Diploma Number | 甲医第1179号
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Granted Date | 2013-11-28
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Degree Name |
Doctor of Medical Science
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Grantor |
Tokushima University
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departments |
Medical Sciences
University Hospital
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