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

Bioessays. 2010 Dec;32(12):1067-76. doi: 10.1002/bies.201000063. Epub 2010 Oct 15.

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.

Publication types

  • Review

MeSH terms

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

Substances

  • CCR6 protein, human
  • Chemokine CCL20
  • Receptors, CCR6