Differential Requirement for CCR6 in IL-23–Mediated Skin and Joint Inflammation

Zhenrui Shi, Emma Garcia-Melchor, Xuesong Wu, Sebastian Yu, Mimi Nguyen, Douglas J. Rowland, Mindy Huynh, Timothy Law, Siba P. Raychaudhuri, Neal L. Millar, Samuel T. Hwang

Research output: Contribution to journalArticle

Abstract

CCR6 is important for the trafficking of IL-17A–producing γδ T cells and required for the development of psoriasiform dermatitis in an IL-23 intradermal injection model. The role of CCR6, however, in IL-23–mediated joint inflammation is unclear. We herein hydrodynamically delivered IL-23 minicircle DNA into wild-type and CCR6-deficient (CCR6-knockout) mice to induce overexpression of IL-23 systemically. After IL-23 gene transfer, wild-type mice exhibited concurrent skin and joint changes that recapitulate some features found in human psoriatic skin and joints. CCR6-knockout mice were resistant to IL-23–induced skin inflammation but exhibited no changes in joint inflammation compared with wild-type mice. Depletion of neutrophils protected wild-type mice from skin and joint disease without suppressing T helper type 17 cytokine expression. In contrast, mice lacking γδ T cells showed a partial reduction in neutrophilic recruitment and a significant decrease in IL-17A expression in skin and paw tissue. Thus, in an IL-23–mediated model that allows concurrent assessment of both skin and joint disease, we showed that CCR6 is critical for inflammation in the skin but not in the joint. Furthermore, our data suggest that neutrophils and γδ T cells are key effector cells in IL-23–mediated skin and joint inflammation in mice.

Original languageEnglish (US)
JournalJournal of Investigative Dermatology
DOIs
StateAccepted/In press - Jan 1 2020

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Shi, Z., Garcia-Melchor, E., Wu, X., Yu, S., Nguyen, M., Rowland, D. J., Huynh, M., Law, T., Raychaudhuri, S. P., Millar, N. L., & Hwang, S. T. (Accepted/In press). Differential Requirement for CCR6 in IL-23–Mediated Skin and Joint Inflammation. Journal of Investigative Dermatology. https://doi.org/10.1016/j.jid.2020.03.965