Ccr6 is dispensable for the development of skin lesions induced by imiquimod despite its effect on epidermal homing of IL-22-producing cells.

Cochez, Perrine [UCL] Michiels, Camille [UCL] Hendrickx, Emilie [UCL] Dauguet, Nicolas [UCL] WARNIER, Guy [UCL] Renauld, Jean-Christophe [UCL] Dumoutier, Laure [UCL]

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. Whereas 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 non-treated 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, where 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.