CCR6 as a possible therapeutic target in psoriasis.
BACKGROUND
Psoriasis is a common, chronic autoimmune disease of the skin. Despite a number of effective treatments, new therapies are needed with enhanced efficacy, safety and convenience. Chemokine receptors are GPCRs that control leukocyte trafficking, and like other GPCRs, are good potential drug targets. The chemokine receptor CCR6 is expressed on the T(H)17 subset of CD4(+) T cells, which produces IL-17A/F, IL-22, TNF-alpha and other cytokines, and which has been implicated in the pathogenesis of psoriasis. CCR6 and its ligand, CCL20/MIP-3alpha, are highly expressed in psoriatic skin and CCR6 is necessary for the pathology induced in a mouse model of psoriasis-like inflammation.


METHODS
This review summarizes the evidence for the importance of the IL-23/T(H)17 axis, and in particular CCR6 and CCL20 in psoriasis, dating from 2000 to the present, and discusses the possibility of inhibiting CCR6 as a treatment for the disease.


RESULTS
The review informs the reader of the current thinking on the mechanisms of inflammation in psoriasis and the possible roles for CCR6 (and CCL20) in disease pathogenesis.


CONCLUSIONS
We conclude that CCR6 should be investigated as a potential therapeutic target in psoriasis.
Hedrick
Michael N
MN
National Institutes of Health, National Institute of Allergy and Infectious Diseases, Laboratory of Molecular Immunology, Inflammation Biology Section, Bethesda, MD 20892, USA.
Lonsdorf
Anke S
AS
Hwang
Sam T
ST
Farber
Joshua M
JM
D000818:Animals; D054418:Chemokine CCL20 / Q000378:metabolism; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D053759:Interleukin-23 / Q000378:metabolism; D051379:Mice; D011565:Psoriasis / Q000188:drug therapy* / Q000503:physiopathology; D054399:Receptors, CCR6 / Q000037:antagonists & inhibitors*
C108355:CCL20 protein, human; D054418:Chemokine CCL20; D053759:Interleukin-23; D054399:Receptors, CCR6