title: Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis.
abstract: Topical application of imiquimod (IMQ), a TLR7/8 ligand and potent immune activator, can induce and exacerbate psoriasis, a chronic inflammatory skin disorder. Recently, a crucial role was proposed for the IL-23/IL-17 axis in psoriasis. We hypothesized that IMQ-induced dermatitis in mice can serve as a model for the analysis of pathogenic mechanisms in psoriasis-like dermatitis and assessed its IL-23/IL-17 axis dependency. Daily application of IMQ on mouse back skin induced inflamed scaly skin lesions resembling plaque type psoriasis. These lesions showed increased epidermal proliferation, abnormal differentiation, epidermal accumulation of neutrophils in microabcesses, neoangiogenesis, and infiltrates consisting of CD4(+) T cells, CD11c(+) dendritic cells, and plasmacytoid dendritic cells. IMQ induced epidermal expression of IL-23, IL-17A, and IL-17F, as well as an increase in splenic Th17 cells. IMQ-induced dermatitis was partially dependent on the presence of T cells, whereas disease development was almost completely blocked in mice deficient for IL-23 or the IL-17 receptor, demonstrating a pivotal role of the IL-23/IL-17 axis. In conclusion, the sole application of the innate TLR7/8 ligand IMQ rapidly induces a dermatitis closely resembling human psoriasis, critically dependent on the IL-23/IL-17 axis. This rapid and convenient model allows further elucidation of pathogenic mechanisms and evaluation of new therapies in psoriasis.
authors.affiliation: Department of Dermatology, Erasmus Medical Center, Rotterdam, The Netherlands. L.vanderfits@lumc.nl
authors.forename: Leslie
authors.initials: L
authors.lastname: van der Fits
authors.forename: Sabine
authors.initials: S
authors.lastname: Mourits
authors.forename: Jane S A
authors.initials: JS
authors.lastname: Voerman
authors.forename: Marius
authors.initials: M
authors.lastname: Kant
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.forename: Ferry
authors.initials: F
authors.lastname: Cornelissen
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mus
authors.forename: Edwin
authors.initials: E
authors.lastname: Florencia
authors.forename: Errol P
authors.initials: EP
authors.lastname: Prens
authors.forename: Erik
authors.initials: E
authors.lastname: Lubberts
mesh_terms: D000634:Aminoquinolines / Q000633:toxicity*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003877:Dermatitis, Contact / Q000276:immunology* / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D000077271:Imiquimod; D018836:Inflammation Mediators / Q000502:physiology*; D020381:Interleukin-17 / Q000378:metabolism / Q000502:physiology*; D053759:Interleukin-23 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011565:Psoriasis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D053722:Receptors, Interleukin-17 / Q000172:deficiency / Q000235:genetics
chemical_list: D000634:Aminoquinolines; D018836:Inflammation Mediators; D020381:Interleukin-17; D053759:Interleukin-23; D053722:Receptors, Interleukin-17; D000077271:Imiquimod