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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
Author
Honjo, Akifumi Department of Respiratory Medicine & Rheumatology, Institute of Health Biosciences, The University of Tokushima Graduate School
Azuma, Masahiko The University of Tokushima KAKEN Search Researchers
Tezuka, Toshifumi The University of Tokushima KAKEN Search Researchers
Biragyn, Arya National Institute on Aging
Keywords
CCR4
TARC-PE38
allergic inflammation
airway hyperresponsiveness
bronchial asthma
Content Type
Thesis or Dissertation
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
ISSN
22125345
NCID
AA12579673
AA12797947
Publisher
The Japanese Respiratory Society|Elsevier
Volume
51
Issue
4
Start Page
241
End Page
249
Published Date
2013-06-22
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
TextVersion
ETD
MEXT report number
甲第2653号
Diploma Number
甲医第1179号
Granted Date
2013-11-28
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences
University Hospital