Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis

TLDR

Topical application of imiquimod (IMQ), a TLR7/8 ligand, can induce psoriasis‑like skin inflammation, and the IL‑23/IL‑17 axis has been implicated in psoriasis. The study aimed to test whether IMQ‑induced dermatitis in mice could model psoriasis‑like disease and to determine its dependence on the IL‑23/IL‑17 axis. IMQ was applied daily to mouse back skin, and disease progression was examined in wild‑type and IL‑23 or IL‑17 receptor‑deficient mice, assessing epidermal changes, immune infiltrates, and cytokine expression. IMQ induced plaque‑like lesions with epidermal hyperplasia, neutrophil microabscesses, neoangiogenesis, and infiltration of CD4⁺ T cells, dendritic cells, and plasmacytoid dendritic cells; IL‑23, IL‑17A, and IL‑17F were upregulated, splenic Th17 cells increased, and disease was almost completely blocked in IL‑23 or IL‑17 receptor‑deficient mice, confirming the pivotal role of the IL‑23/IL‑17 axis.

Abstract

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.