Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Podcasts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Podcasts
  • Subscriptions

Mechanism of long-lasting suppression against Th2 immune response in the lung by a novel antedrug TLR7 agonist

Kazuo Eiho, Hiroyuki Matsui, Hideyuki Hayashi, Ryosaku Inagaki, Mikio Aoki, Mark Biffen, Andrew Leishman, Susan Edwards, Clare Murray, Haruo Takaku, Hideyuki Tomizawa, Shizuo Akira, Yutaka Ueda
European Respiratory Journal 2011 38: p1842; DOI:
Kazuo Eiho
1Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroyuki Matsui
1Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hideyuki Hayashi
1Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryosaku Inagaki
1Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mikio Aoki
1Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark Biffen
2Bioscience, AstraZeneca R&D Charnwood, Loughborough, Leicestershire, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew Leishman
2Bioscience, AstraZeneca R&D Charnwood, Loughborough, Leicestershire, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susan Edwards
2Bioscience, AstraZeneca R&D Charnwood, Loughborough, Leicestershire, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Clare Murray
2Bioscience, AstraZeneca R&D Charnwood, Loughborough, Leicestershire, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Haruo Takaku
1Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hideyuki Tomizawa
1Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shizuo Akira
3Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yutaka Ueda
1Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
Loading

Abstract

Rationale: To identify the mechanisms by which a novel antedrug Toll like receptor 7 (TLR7) agonist, AZ12441970, mediates the long-lasting suppression of Th2 immune responses.

Methods: Long-lasting efficacy of AZ12441970 against bronchoalveolar lavage (BAL) eosinophilia was investigated utilizing Ovalbumin (OVA)/Alum-sensitised mice or OVA-specific Th2 cells adoptively transferred into mice. The mechanism by which AZ12441970 mediated long-lasting efficacy was investigated utilizing T cell-deficient nude mice and several knock-out (KO) mice including type I IFN receptor KO mice, B cell KO mice and rag2 KO mice lacking B and T cells.

Results: Weekly lung doses of AZ12441970 for 6 weeks significantly inhibited BAL eosinophilia for at least 6 weeks following cessation of dosing. The long-lasting efficacy observed with the compound was largely abolished in type I IFN receptor KO mice, rag2 KO mice or nude mice, but maintained in B cell KO mice. T cells were shown to be involved in the mechanism of efficacy in a T cell reconstituted nude mouse model of allergic airways inflammation. Nose only exposure of AZ12441970 also resulted in long-term efficacy in the lung.

Conclusions: We show that intranasal dosing of AZ12441970 to achieve lung exposure in mice induces a long-lasting efficacy against Th2 immune responses in the lung. The efficacy in the lung is also achieved by nose only exposure of the TLR7 agonist. Furthermore, our mechanism studies demonstrate that the long-lasting inhibition of the Th2 immune responses with the compound is IFN-α- and T-cell-dependent. These data suggest that novel antedrug TLR7 agonists may have potential in the treatment of allergic disease.

  • © 2011 ERS
Previous
Back to top
Vol 38 Issue Suppl 55 Table of Contents
  • Table of Contents
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Mechanism of long-lasting suppression against Th2 immune response in the lung by a novel antedrug TLR7 agonist
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Mechanism of long-lasting suppression against Th2 immune response in the lung by a novel antedrug TLR7 agonist
Kazuo Eiho, Hiroyuki Matsui, Hideyuki Hayashi, Ryosaku Inagaki, Mikio Aoki, Mark Biffen, Andrew Leishman, Susan Edwards, Clare Murray, Haruo Takaku, Hideyuki Tomizawa, Shizuo Akira, Yutaka Ueda
European Respiratory Journal Sep 2011, 38 (Suppl 55) p1842;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Mechanism of long-lasting suppression against Th2 immune response in the lung by a novel antedrug TLR7 agonist
Kazuo Eiho, Hiroyuki Matsui, Hideyuki Hayashi, Ryosaku Inagaki, Mikio Aoki, Mark Biffen, Andrew Leishman, Susan Edwards, Clare Murray, Haruo Takaku, Hideyuki Tomizawa, Shizuo Akira, Yutaka Ueda
European Respiratory Journal Sep 2011, 38 (Suppl 55) p1842;
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo

Jump To

  • Article
  • Info & Metrics
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

  • Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis
  • Farm dust decreases Th2 driven allergic airway inflammation in mice: A role for airway TLR2 and TLR4?
Show more 226. T-cell subsets

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Reviewers
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2023 by the European Respiratory Society