Background/purpose(s): Psoriasis is a skin-specific autoimmune disease that causes scaling, erythema and thickening. The disease involves immune cell infiltration and keratinocyte proliferation in skin lesions. Previous studies have demonstrated that Th17 cells and IL-22 play prominent roles in the pathogenesis of psoriasis via IL-17, IL-22 and IL-23 signaling. However, the role of innate cells in this process remains unclear.
Methods: In this study, using the TLR7/8 agonist imiquimod (IMQ) in a well-established murine model, we demonstrated that natural killer (NK) cells play an important role in the pathogenesis of psoriasis. Non-obese diabetic (NOD) mice are prone to Th1 and Th17 responses, and the lack of NK cell activity and macrophages in these animals contribute to their value as a model for type I diabetes.
Results: The NOD mice treated with IMQ (NOD-IMQ) exhibit markedly attenuated skin lesions compared to BALB/c mice treated with IMQ (BALB/c-IMQ). An analysis of immune cell types revealed that the number of macrophages, plasmacytoid dendritic cells (pDCs), neutrophils and Th1, Th2, Th17, Treg, and NK cells increased in the BALB/c-IMQ mice compared to the NOD-IMQ mice. Testing NK cell activity and macrophage function, NK cell cytotoxicity and macrophage phagocytosis, but not macrophage migration, were decreased in the NOD mice compared with the BALB/c mice. After NK cell depletion, normal BALB/c-IMQ mice exhibited milder skin lesions than the NOD-IMQ mice.
Conclusion: These results suggest that NK cells play a critical role in IMQ-induced skin inflammation. Controlling NK cell activity may be a potential therapeutic approach for psoriasis.
Keywords: Imiquimod; Natural killer cells; Non-obese diabetic mice; Psoriasis.
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