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.
School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia. iain.comerford@adelaide.edu.au
Iain
I
Comerford
Mark
M
Bunting
Kevin
K
Fenix
Sarah
S
Haylock-Jacobs
Wendel
W
Litchfield
Yuka
Y
Harata-Lee
Michelle
M
Turvey
Julie
J
Brazzatti
Carly
C
Gregor
Phillip
P
Nguyen
Ervin
E
Kara
Shaun R
SR
McColl
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