title: IL-22 is required for imiquimod-induced psoriasiform skin inflammation in mice.
abstract: Psoriasis is a common chronic autoimmune skin disease of unknown cause that involves dysregulated interplay between immune cells and keratinocytes. IL-22 is a cytokine produced by the TH1, TH17, and TH22 subsets that are functionally implicated in the psoriatic pathology. We assessed the role of IL-22 in a mouse model where psoriasiform skin inflammation is triggered by topical application of the TLR7/8 agonist imiquimod. At the macroscopic level, scaly skin lesions induced by daily applications of imiquimod in wild-type mice were almost totally absent in IL-22-deficient mice or in mice treated with a blocking anti-IL-22 Ab. At the microscopic level, IL-22-deficient mice showed a dramatic decrease in the development of pustules and a partial decrease in acanthosis. At the molecular level, the absence or inhibition of IL-22 strongly decreased the expression of chemotactic factors such as CCL3 and CXCL3 and of biomarkers such as S100A8, S100A7, and keratin 14, which reflect the antimicrobial and hyperproliferative responses of keratinocytes. IL-22 also played a major role in neutrophil infiltration after imiquimod treatment. IL-23 was required for IL-22 production, and γδ TCR lymphocytes represented the major source of IL-22 in lymph nodes from imiquimod-treated mice. However, T cells were not absolutely required for IL-22 production because imiquimod-induced IL-22 expression in the skin is still preserved in Rag2(-/-) mice. Taken together, our data show that IL-22 is required for psoriasis-like lesions in the mouse imiquimod model and is produced by both T cells and innate immune cells.
authors: Ludwig Institute for Cancer Research, B-1200 Brussels, Belgium.
authors: Astrid B
authors: AB
authors: Van Belle
authors: Magali
authors: M
authors: de Heusch
authors: Muriel M
authors: MM
authors: Lemaire
authors: Emilie
authors: E
authors: Hendrickx
authors: Guy
authors: G
authors: Warnier
authors: Kyri
authors: K
authors: Dunussi-Joannopoulos
authors: Lynette A
authors: LA
authors: Fouser
authors: Jean-Christophe
authors: JC
authors: Renauld
authors: Laure
authors: L
authors: Dumoutier
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects* / Q000494:pharmacology; D000634:Aminoquinolines / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054405:Chemokine CCL3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003872:Dermatitis / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D000077271:Imiquimod; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011565:Psoriasis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000943:Antigens, Differentiation; D054405:Chemokine CCL3; D000077271:Imiquimod; D007378:Interleukins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000097043:Interleukin-22; C496534:Ccl3 protein, mouse