An immune paradox: how can the same chemokine axis regulate both immune tolerance and activation?: CCR6/CCL20: a chemokine axis balancing immunological tolerance and inflammation in autoimmune disease

Iain Comerford, Mark D Bunting, Kevin Fenix, Sarah Haylock-Jacobs, Wendel Litchfield, Yuka Harata-Lee, Michelle Turvey, Julie Brazzatti, Carly Gregor, Phillip Nguyen, Ervin Kara, Shaun R McColl

Research output: Contribution to journalReview articlepeer-review

93 Citations (Scopus)

Abstract

Chemokines (chemotactic cytokines) drive and direct leukocyte traffic. New evidence suggests that the unusual CCR6/CCL20 chemokine receptor/ligand axis provides key homing signals for recently identified cells of the adaptive immune system, recruiting both pro-inflammatory and suppressive T cell subsets. Thus CCR6 and CCL20 have been recently implicated in various human pathologies, particularly in autoimmune disease. These studies have revealed that targeting CCR6/CCL20 can enhance or inhibit autoimmune disease depending on the cellular basis of pathogenesis and the cell subtype most affected through different CCR6/CCL20 manipulations. Here, we discuss the significance of this chemokine receptor/ligand axis in immune and inflammatory functions, consider the potential for targeting CCR6/CCL20 in human autoimmunity and propose that the shared evolutionary origins of pro-inflammatory and regulatory T cells may contribute to the reason why both immune activation and regulation might be controlled through the same chemokine pathway.

Original languageEnglish
Pages (from-to)1067-76
Number of pages10
JournalBioEssays
Volume32
Issue number12
DOIs
Publication statusPublished or Issued - Dec 2010
Externally publishedYes

Keywords

  • Adaptive Immunity
  • Autoimmune Diseases/immunology
  • Chemokine CCL20/immunology
  • Humans
  • Immune Tolerance
  • Inflammation/immunology
  • Receptors, CCR6/immunology
  • T-Lymphocytes/immunology
  • T-Lymphocytes, Regulatory/metabolism
  • Th17 Cells/metabolism

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