CCR6 is required for IL-23–induced psoriasis-like inflammation in mice
Michael N. Hedrick, … , Sam T. Hwang, Joshua M. Farber
Michael N. Hedrick, … , Sam T. Hwang, Joshua M. Farber
Published July 6, 2009
Citation Information: J Clin Invest. 2009;119(8):2317-2329. https://doi.org/10.1172/JCI37378.
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Research Article Dermatology

CCR6 is required for IL-23–induced psoriasis-like inflammation in mice

Abstract

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.

Authors

Michael N. Hedrick, Anke S. Lonsdorf, Aiko-Konno Shirakawa, Chyi-Chia Richard Lee, Fang Liao, Satya P. Singh, Hongwei H. Zhang, Alexander Grinberg, Paul E. Love, Sam T. Hwang, Joshua M. Farber

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Figure 7

Il22 mRNA correlates with IL-23–induced inflammation, but not with Il17a and Il17f mRNA, and is produced in T cell–independent and T cell–dependent phases.

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Il22 mRNA correlates with IL-23–induced inflammation, but not with Il17...
(A–C) Ears were injected as in Figure 1, and mRNAs for Il22 (A), Il17a (B), Il17f (C), and Gapdh were measured at days 5 and 15 by real-time RT-PCR. Data are Gapdh-normalized fold changes versus the PBS-injected sample with the greatest ΔCt, from 3 mice/group in 1 representative experiment of 2. Note that values cannot be compared between plots. *P < 0.05 vs. IL-23 Ccr6–/–; #P < 0.05 vs. IL-23 Rag1–/–. Other pairwise comparisons between the IL-23–injected groups did not yield significant differences.