A Chronic Psoriasis Model Using Long-Term Imiquimod Application in IL-10-Deficient Mice: Recapitulating Skin Inflammation, Comorbidities, and Gut-Skin Axis Alterations.

BACKGROUND

Psoriasis is a persistent systemic inflammatory condition mediated by the interleukin (IL)-23/IL-17 signaling pathway. Existing murine models, including imiquimod (IMQ)-applied wild-type (WT) mice, may not reflect chronicity and systemic comorbidities of psoriasis, particularly gut-related manifestations linked to the gut-skin axis.

OBJECTIVE

To establish a murine model that more accurately reflects chronic psoriasis, its systemic comorbidities, and associated gut environment alterations.

METHODS

C57BL/6 IL-10-deficient (IL-10 knockout [KO]) and WT mice received topical IMQ or vehicle for 6 weeks. Subsequently, tissue samples from skin, colon, joints, kidneys, liver, abdominal aortas, lymph nodes, and spleens, as well as fecal and blood samples, were collected for histopathologic, immunologic, gut environment analysis.

RESULTS

IMQ-treated IL-10 KO mice developed prolonged psoriatic inflammatory responses with increased epidermal thickness and higher infiltration of CD45+, myeloperoxidase+, and IL-17+ cells. They also exhibited early-onset, severe colitis with marked weight loss, shortened colon length, and elevated colitis severity scores. While IMQ induced systemic inflammation in multiple organs, IL-10 KO mice did not show more severe joint, liver, or kidney involvement than WT mice. Elevated serum tumor necrosis factor alpha and plasminogen activator inhibitor-1 levels, increased heart/body weight ratio, enhanced gut permeability, and distinct gut microbiota profiles were observed in IL-10 KO mice.

CONCLUSION

The 6-week IMQ-applied IL-10 KO model may better reflect chronic and severe psoriasis with gut-related comorbidities, offering a valuable platform to investigate the gut-skin axis.