Background/Purpose: Psoriasis is an inflammatory skin disease that progresses and worsens if left unattended. IL17 plays a pivotal role as a pathogenic trigger. Despite Th17 cells, keratinocytes also serve as a significant source of IL17 in the skin. These cells adopt immune-like behavior when exposed to inflammatory stimuli. Yet, the precise factors and mechanisms prompting this transition remain unclear. Here, we investigated the involvement of YY1 in determining this transition using the in vitro psoriasis disease model.

Methods: An invitro psoriasis like model was developed by exposing Keratinocyte (HaCat cell line) cells to imiquimod. Treated cells were analyzed for enhanced inflammation (IL17/IL23) and proliferation (INV, KRT5, FLG, and KRT14) by RTPCR and MTT assay. The expression of YY1 was also noted in treated cells using RTPCR and WB. To establish a relationship with YY1 and IL17/IL23 axis, YY1 was overexpressed in the cells and processed further to analyze the alteration in the expression of IL17/IL23 using RTPCR and WB. For confirmation, we also knocked down YY1 in the presence of imiquimod and analyzed cells for IL17/IL23 expression.

Results: Imiquimod treated HaCat cells became inflammatory and hyperproliferative after 48 hours of incubation. The expression of IL17 and IL23 was 3-fold and 2-fold higher in the treated cell than the control. There was also a significant increase in INV, KRT5, FLG, and KRT14 expression. We also observed about 3.5-fold higher expression of YY1 in the treated cells. To confirm the YY1-IL17/IL23 relation, the induced YY1 overexpression was able to enhance the IL17 expression by 6-fold and the IL-23 expression by 4.5-fold. Similarly, in imiquimod YY1 knockout cells along with YY1, IL17/IL23 expression was also reduced.

Conclusion: The findings of this study highlight that the therapeutic intervention of YY1 can aid in controlling psoriasis. YY1 is in direct association with disease exacerbating cytokines like IL17/IL23. Targeting these through YY1 can be an alternative approach.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/yy1-a-potential-modulator-of-il17-il23-axis-in-psoriasis-disease/