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

Published on Dec 1, 2020in Journal of Investigative Dermatology7.143
· DOI :10.1016/J.JID.2020.03.965
Zhenrui Shi9
Estimated H-index: 9
(UC Davis: University of California, Davis),
Emma Garcia-Melchor4
Estimated H-index: 4
(Glas.: University of Glasgow)
+ 8 AuthorsSamuel T Hwang49
Estimated H-index: 49
(UC Davis: University of California, Davis)
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Abstract
Abstract CC chemokine receptor 6 (CCR6) is important for the trafficking of IL-17A-producing γδ T cells and required for the development of psoriasiform dermatitis (PsD) 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 (WT) and CCR6-deficient (CCR6-KO) mice to induce overexpression of IL-23 systemically. After IL-23 gene transfer, WT mice exhibited concurrent skin and joint changes that recapitulate some features found in human psoriatic skin and joints. CCR6-KO mice were resistant to IL-23-induced skin inflammation but exhibited no changes in joint inflammation compared to WT mice. Depletion of neutrophils protected WT mice from skin and joint disease without suppressing Th17 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.
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