AhR and Ccr6 are not required for IL-22 production in the imiquimod-induced psoriasis model
(2016)
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- Abstract
- IL-22 is a crucial cytokine in skin homeostasis by its action on keratinocytes. It induces the production of antimicrobial peptides, promotes epithelial regeneration and therefore plays an important role in wound healing. However, when the effects of IL-22 are not controlled, they can lead to chronic inflammatory processes such as psoriasis. Psoriasis is a chronic inflammatory skin disease, affecting 1,5% of the Caucasian population, characterized by red, itchy and scaly patches and causing life discomfort. Currently, psoriasis treatments allow to control the symptoms but no treatment exists to cure this pathology. Previous studies have shown that IL-22 is a key player in this disease, as suggested by its increased expression in the skin and the blood of psoriatic patients. A better understanding of the molecules regulating IL-22 production might therefore open important perspectives. The goal of our study was to investigate the role of two factors associated with IL-22-producing cells: AhR and Ccr6. AhR is a transcription factor controlling IL-22 production by several cell types, including Th17 cells in vitro, whereas Ccr6 is a chemokine receptor required for IL-22 production in the IL-23-induced psoriasis model. In our first study based on the imiquimod-induced psoriasis model, we showed that IL-22 is mainly produced by γδ T cells and a novel IL-22-producing cell type identified in this model, CD4- CD8- TCRβ+ cells. Moreover, Th17 cells and ILC3s are also able to produce IL-22 under certain conditions. Our results demonstrate that AhR is required for IL-22 production in the epidermis by Th17 cells. However, for γδ T cells, CD4- CD8- TCRβ+ cells and ILC3s, AhR deficiency does not directly affect IL-22 production but decreases the recruitment or the local proliferation of the cells. Our second study on Ccr6 highlighted that, in the imiquimod model, this factor is not required for IL-22 production in total skin as well as for skin lesion development. However, Ccr6-deficient mice display a lower Il22 expression specifically in the epidermis, associated with a lack of γδ T cell recruitment. Moreover, in an ex vivo stimulation model, we demonstrated that Il22 expression depends on Ccr6 in epidermal but not in dermal cells. In this ex vivo system, we showed that Ccr6 is required for the epidermis homing of γδ T cells and ILCs, representing the main potential source of IL-22 in normal and T cell deficient mice, respectively. Taken together, our data indicate that neither AhR nor Ccr6 directly affect the IL-22 production in the skin. However, these two factors indirectly induce Il22 expression by controlling the presence of the IL-22-producing cells in the skin.
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Cochez, P. (2016). AhR and Ccr6 are not required for IL-22 production in the imiquimod-induced psoriasis model. https://hdl.handle.net/2078.5/75842