A Chronic Psoriasis Model Using Long-Term Imiquimod Application in IL-10-Deficient Mice: Recapitulating Skin Inflammation, Comorbidities, and Gut–Skin Axis Alterations
10.5021/ad.25.108
- Author:
Jee Hyun KIM
;
Soo Ran LEE
;
Hyun Keun AHN
;
Hyun Taek HONG
;
Ui Hyeon JO
;
Jong Pil IM
;
Joo Sung KIM
;
Min Jung KIM
;
Jeonghwan LEE
;
Jeong Hwan PARK
;
Hyunsun PARK
;
Seong-joon KOH
- Publication Type:Original Article
- From:Annals of Dermatology
2025;37(6):383-396
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
