Abstract
Antigen presentation plays a critical role in the pathogenesis of immune-mediated disorders. This study aimed to investigate the effects of IFN-γ and a cytokine mix (5MIX: IL-1α, IL-17A, IL-22, OsM, and TNF-α) on the antigen-presenting capabilities of keratinocytes, with a specific focus on immune-mediated dermatological conditions such as psoriasis (Ps). To achieve this, keratinocytes were treated with IFN-γ and 5MIX, and their impact on the expression of key antigen-presentation molecules, HLA-DRα and CD74, was assessed. Transcriptomic analysis revealed that IFN-γ alone altered the expression of 254 genes, highlighting its central role in modulating immune responses, including the recruitment of immune cells and regulation of inflammation. Temporal experiments further demonstrated that IFN-γ and 5MIX enhanced early endocytic activity and lysosomal degradation pathways, both essential for effective antigen presentation and T-cell activation. To extend these findings to a clinical context, a co-culture model using keratinocytes derived from psoriatic patients was established. This model revealed increased cytokine production following antigen stimulation, indicating robust and consistent CD4+ and naïve T-cell responses. These results elucidate the complex dynamics of cytokine signaling and antigen presentation in keratinocytes, providing insights into potential therapeutic strategies for immune-mediated skin disorders like Ps.