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.
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.
Comerford
Iain
I
School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia. iain.comerford@adelaide.edu.au
Bunting
Mark
M
Fenix
Kevin
K
Haylock-Jacobs
Sarah
S
Litchfield
Wendel
W
Harata-Lee
Yuka
Y
Turvey
Michelle
M
Brazzatti
Julie
J
Gregor
Carly
C
Nguyen
Phillip
P
Kara
Ervin
E
McColl
Shaun R
SR
D056704:Adaptive Immunity; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D054418:Chemokine CCL20 / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology*; D054399:Receptors, CCR6 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism
C106311:CCR6 protein, human; D054418:Chemokine CCL20; D054399:Receptors, CCR6