Honjo, Akifumi Department of Respiratory Medicine & Rheumatology, Institute of Health Biosciences, The University of Tokushima Graduate School
Ogawa, Hirohisa The University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Azuma, Masahiko The University of Tokushima KAKEN Search Researchers
Tezuka, Toshifumi The University of Tokushima KAKEN Search Researchers
Sone, Saburo The University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Biragyn, Arya National Institute on Aging
Nishioka, Yasuhiko The University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Thesis or Dissertation
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.
The Japanese Respiratory Society|Elsevier
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。
|DOI (Published Version)|
|URL ( Publisher's Version )|
LID201312091001.pdf 165 KB
LID201405271002.pdf 1.27 MB
|MEXT report number||
Doctor of Medical Science