Ccr6 Is Dispensable for the Development of Skin Lesions Induced by Imiquimod despite its Effect on Epidermal Homing of IL-22-Producing Cells.

Abstract

Expression of the chemokine receptor Ccr6 is shared by most IL-22-producing cells, and Ccr6-deficient mice showed decreased IL-22 production and skin inflammation upon IL-23 intradermal injections. To determine whether this observation might be extended to another psoriasis model, we applied imiquimod on Ccr6-deficient mice. Although epidermal IL-22 production was decreased because of a deficient recruitment of γδ T cells in these mice, they were not protected against psoriatic lesions. When primary epidermis or dermis tissue culture cells from nontreated mice were stimulated ex vivo with IL-1α/IL-2/IL-23, we observed that Ccr6 is crucial for Il22 expression from epidermal but not dermal cultures. Taking advantage of Ccr6-LacZ-knock-in mice, we showed that Ccr6 is necessary for the homing of Ccr6-positive cells, probably a γδ T-cell subset, which represents the main potential IL-22 source in the epidermis. Similar results were observed in Rag1-/- epidermis and dermis primary cultures, in which a subset of innate lymphoid cells expressing Ccr6 represents the main potential source of IL-22. Taken together, our data show that Ccr6 is not required for the development of skin lesions induced by imiquimod despite its effect on epidermal homing of IL-22-producing cells.

• Authors: Perrine M Cochez, Camille Michiels, Emilie Hendrickx, Nicolas Dauguet, Guy Warnier, Jean-Christophe Renauld, Laure Dumoutier
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 137 Issue 5 Pg. 1094-1103 (05 2017) ISSN: 1523-1747 [Electronic] United States
• PMID: 28115058 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Aminoquinolines
• CCR6 protein, mouse
• Homeodomain Proteins
• Interleukins
• Receptors, CCR6
• RAG-1 protein
• beta-Galactosidase
• Imiquimod

Topics

• Aminoquinolines (toxicity)
• Animals
• Cells, Cultured
• Disease Models, Animal
• Epidermis (drug effects, immunology, pathology)
• Gene Knock-In Techniques
• Homeodomain Proteins (genetics)
• Imiquimod
• Interleukins (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Psoriasis (chemically induced, immunology, pathology)
• Receptors, CCR6 (genetics)
• T-Lymphocyte Subsets (immunology)
• beta-Galactosidase (genetics)
• Interleukin-22