CCR6 is required for IL-23-induced  psoriasis-like inflammation in mice.
Psoriasis is a common immune-mediated chronic inflammatory skin disorder, but the mechanisms of pathogenesis are still poorly understood. IL-23 is expressed in psoriatic skin, and IL-23 injection produces IL-22-dependent psoriasiform changes in mouse skin. Th17 cells produce IL-22 and display CCR6, the CCL20 receptor; CCR6+ T cells and CCL20 are abundant in psoriatic skin. We investigated a possible role for CCR6 in recruiting Th17 cells and producing psoriasiform pathology by injecting IL-23 into the skin of WT and Ccr6-/- mice. Unlike for WT mice, IL-23-injected ears of Ccr6-/- mice showed neither substantial epidermal/dermal changes nor increased Il22 mRNA expression. However, injection of IL-22 yielded equivalent psoriasiform changes in WT and Ccr6-/- mice. Surprisingly, IL-23-injected ears of WT and Ccr6-/- mice contained similar numbers of Th cells able to make IL-17A and/or IL-22. Furthermore, in ears of Rag1-/- mice, IL-23 initially induced skin changes and levels of Il22 mRNA that were indistinguishable from WT mice, revealing at least one non-T cell source for IL-22. We conclude that CCR6 is essential in a model of IL-23-induced, IL-22-mediated dermatitis, which develops in sequential T cell-independent and T cell-dependent phases. These findings reveal an expanded role for CCR6 in IL-23-related responses and identify CCR6 as a potential therapeutic target in psoriasis.
Hedrick
Michael N
MN
Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA.
Lonsdorf
Anke S
AS
Shirakawa
Aiko-Konno
AK
Richard Lee
Chyi-Chia
CC
Liao
Fang
F
Singh
Satya P
SP
Zhang
Hongwei H
HH
Grinberg
Alexander
A
Love
Paul E
PE
Hwang
Sam T
ST
Farber
Joshua M
JM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D003713:Dendritic Cells / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology; D020381:Interleukin-17 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000633:toxicity*; D007378:Interleukins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D011565:Psoriasis / Q000209:etiology*; D054399:Receptors, CCR6 / Q000502:physiology*; D000097043:Interleukin-22
D018398:Homeodomain Proteins; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D054399:Receptors, CCR6; D000097043:Interleukin-22; C498126:CCR6 protein, mouse; C064658:RAG-1 protein