Abstract
BACKGROUND: Psoriasis is a chronic, inflammatory autoimmune skin disease, characterized by epidermal hyperplasia and abnormal immune system activation. It is influenced by both genetic and environmental factors. METHODS: We identified hub genes associated with activated CD8 + T cell infiltration in psoriatic skin using machine learning algorithms. A LASSO regression model for psoriasis diagnosis was constructed based on these hub genes. Single-cell analysis identified a UBE2T+ Keratinocyte subpopulation, and spatial transcriptomics determined its location in the stratum spinosum. Additionally, in vitro experiments were conducted using a psoriatic keratinocyte cell model to assess the expression levels of UBE2T and its impact on cell proliferation and IL23A expression. RESULTS: Activated CD8 + T cells were significantly infiltrated in psoriatic skin. UBE2T was identified as a hub gene linked to activated CD8 + T cell infiltration. The UBE2T+ Keratinocyte subpopulation was located in the stratum spinosum of the epidermis, with the potential to differentiate into the UBE2T- Keratinocyte subpopulation. In vitro, UBE2T overexpression in HaCaT cells led to increased proliferation and upregulation of IL23A, a key pro-inflammatory factor. CONCLUSIONS: UBE2T may serve as a potential diagnostic marker for psoriasis. The UBE2T+ Keratinocyte subpopulation is associated with excessive keratinocyte proliferation and inflammation, suggesting it could be a prospective target for psoriasis treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-026-07840-9.