Go to The Journal of Clinical Investigation
Insight white on transparent.20160208
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All...
  • Collections
    • Recently published
    • Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

Insight white on transparent small

  • About
  • Editors
  • Consulting Editors
  • For authors
  • Transfers
  • Current issue
  • Past issues
  • By specialty
  • Contact
  • Recently published
  • Technical Advances
  • Clinical Medicine
  • Editorials
  • Top read articles
Essential role for CCR6 in certain inflammatory diseases demonstrated using specific antagonist and knockin mice
Remy Robert, … , Claude C.A. Bernard, Charles R. Mackay
Remy Robert, … , Claude C.A. Bernard, Charles R. Mackay
Published August 3, 2017
Citation Information: JCI Insight. 2017;2(15):e94821. doi:10.1172/jci.insight.94821.
View: Text | PDF
Categories: Research Article Therapeutics

Essential role for CCR6 in certain inflammatory diseases demonstrated using specific antagonist and knockin mice

  • Text
  • PDF
Abstract

The chemokine receptor CCR6 marks subsets of T cells and innate lymphoid cells that produce IL-17 and IL-22, and as such may play a role in the recruitment of these cells to certain inflammatory sites. However, the precise role of CCR6 has been controversial, in part because no effective monoclonal antibody (mAb) inhibitors against this receptor exist for use in mouse models of inflammation. We circumvented this problem using transgenic mice expressing human CCR6 (hCCR6) under control of its native promoter (hCCR6-Tg/mCCR6–/–). We also developed a fully humanized mAb against hCCR6 with antagonistic activity. The expression pattern of hCCR6 in hCCR6-Tg/mCCR6–/– mice was consistent with the pattern observed in humans. In mouse models of experimental autoimmune encephalomyelitis (EAE) and psoriasis, treatment with anti-hCCR6 mAb was remarkably effective in both preventive and therapeutic regimens. For instance, in the imiquimod model of psoriasis, anti-CCR6 completely abolished all signs of inflammation. Moreover, anti-hCCR6 attenuated clinical symptoms of myelin oligodendrocyte glycoprotein–induced (MOG-induced) EAE and reduced infiltration of inflammatory cells in the central nervous system. CCR6 plays a critical role in Th17 type inflammatory reactions, and CCR6 inhibition may offer an alternative approach for the treatment of these lesions.

Authors

Remy Robert, Caroline Ang, Guizhi Sun, Laurent Juglair, Ee X. Lim, Linda J. Mason, Natalie L. Payne, Claude C.A. Bernard, Charles R. Mackay

×

Full Text PDF | Download (3.83 MB)

Follow JCI Insight: Facebook logo white Twitter logo v2 Rss icon
Copyright © 2018 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts