Elucidating the role of dendritic cells and b cells in imiquimod (IMQ)-induced psoriasis-like mouse model

• मुख्य लेखक: Noor, Aina Akmal Mohd
• स्वरूप: थीसिस
• भाषा: अंग्रेज़ी
• प्रकाशित: 2025
• विषय: R Medicine; RA440-440.87 Study and teaching. Research
• ऑनलाइन पहुंच: http://eprints.usm.my/63167/

Psoriasis is a chronic inflammatory skin disorder characterised by keratinocyte hyperproliferation and immune dysregulation. Although psoriasis is a T cell-mediated disease, increasing evidence suggests the important roles of dendritic cells (DCs) and B cells in initiating, sustaining and regulating psoriatic inflammation. Therefore, this study aims to elucidate the roles of DCs and B cells in an imiquimod (IMQ)-induced psoriasis-like mouse model through a time-based analysis of immune responses in the skin, spleen and blood. BALB/c mice were divided into control (n=6) and IMQ-induced (n=6) groups, with samples collected on day 3, day 5 and day 7. Psoriasis-like inflammation was induced via topical IMQ application, leading to increased skinfold thickness, modified Psoriasis Area and Severity Index (PASI) scores and splenomegaly compared to controls. Histological analysis (hematoxylin and eosin (H&E) and Masson’s trichrome staining) revealed hallmark psoriasis features, including epidermal hyperplasia, hyperkeratosis, immune cell infiltration and visible blood vessel observation, as well as increased immune cell density in the spleen. Notably, the white pulp of the spleen exhibited significant germinal centre (GC) enlargement, indicating heightened lymphoid activity. Flow cytometry was used to analyse DC and B cell dynamics across samples. The results demonstrated an increasing trend in CD11chi/+MHCII+ DC populations across all samples, accentuating their involvement in antigen presentation and immune activation. Concurrently, B220+CD38+ B cells increased in the spleen, while CD19+CD38+ B cells were significantly higher in the skin but decreased in the blood, suggesting distinct migration and activation dynamics. Subsequent gene expression analysis (RT-PCR) of CD11c, H2-Aa, BAFF, IL-10, IL-6 and CXCR5 revealed consistent upregulation in the IMQ-induced group, supporting a sustained inflammatory state driven by DC and B cell activation. ELISA-based cytokine analysis showed elevated serum levels of BAFF, IL-10 and IL-6 at each time point, further reinforcing their role in chronic inflammation and B cell activation. Overall, the increment of DC and B cell markers at both cellular and molecular levels, accompanied by elevated pro- and anti-inflammatory cytokines, reflects a robust and evolving immune response. These findings affirm the successful establishment of the IMQ-induced psoriasis-like mouse model and support the study objectives in elucidating the dynamic involvement of DCs and B cells during disease progression as well as offering a foundation for future therapeutic research