Psoriasis is a chronic immune-mediated inflammatory skin disease. A key pathway in psoriasis is the IL-23/Th17 axis, which increases inflammatory cytokines such as IL-17A, IL-17F, and IL-22. These signals activate keratinocytes and can weaken the epidermal barrier, the outer protective layer of the skin. Barrier-related genes such as FLG/filaggrin and LOR/loricrin are important for maintaining normal skin structure and protection.

In this study, we examined whether baricitinib, a JAK1/2 inhibitor, can reduce IL-23-driven psoriasiform inflammation and restore epidermal barrier gene expression. We used three complementary models: an ex vivo murine skin and lymph node co-culture model stimulated with recombinant IL-23, an in vivo IL-23 minicircle mouse model, and HaCaT human keratinocytes.

Across these models, IL-23 stimulation increased Th17 cytokine expression and reduced structural barrier genes. Baricitinib suppressed IL-23-induced inflammatory responses and increased barrier-associated genes, including FLG/filaggrin and LOR/loricrin. In HaCaT keratinocytes, baricitinib increased FLG expression without major changes in proliferation or apoptosis markers, suggesting a possible direct effect on keratinocyte barrier regulation.

These findings suggest that baricitinib may improve psoriatic disease not only by suppressing inflammatory cytokine signaling, but also by promoting recovery of epidermal barrier gene expression.