title: 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.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium; de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Perrine M
authors.initials: PM
authors.lastname: Cochez
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium; de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Camille
authors.initials: C
authors.lastname: Michiels
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium; de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Emilie
authors.initials: E
authors.lastname: Hendrickx
authors.affiliation: de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dauguet
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Warnier
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium; de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium; de Duve Institute, Université catholique de Louvain, Brussels, Belgium. Electronic address: laure.dumoutier@uclouvain.be.
authors.forename: Laure
authors.initials: L
authors.lastname: Dumoutier
mesh_terms: D000634:Aminoquinolines / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004817:Epidermis / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D055879:Gene Knock-In Techniques; D018398:Homeodomain Proteins / Q000235:genetics; D000077271:Imiquimod; D007378:Interleukins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011565:Psoriasis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D054399:Receptors, CCR6 / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D001616:beta-Galactosidase / Q000235:genetics; D000097043:Interleukin-22
chemical_list: D000634:Aminoquinolines; D018398:Homeodomain Proteins; D000077271:Imiquimod; D007378:Interleukins; D054399:Receptors, CCR6; D001616:beta-Galactosidase; D000097043:Interleukin-22; C498126:CCR6 protein, mouse; C064658:RAG-1 protein