PhD Scientific Days 2026

Poster Session 2.B - Molecular Medicine

The effect of JAK inhibitor baricitinib in experimental autoimmune skin blistering

Name of the presenter

Koncz, Petra

Institute/workplace of the presenter

Department of Physiology

Authors

Petra Koncz¹, Réka Mátó¹, Attila Mócsai²
1: Department of Physiology, Semmelweis University Faculty of Medicine
2: Department of Physiology, Semmelweis University Faculty of Medicine; HUN-REN-SU Inflammation Physiology Research Group

Text of the abstract

Introduction: Subepidermal autoimmune skin blistering diseases are characterized by autoantibody formation against components of the dermal-epidermal junction, leading to activation of inflammatory cells and consequent dissociation of the dermo-epidermal junction. Baricitinib is a small molecule JAK inhibitor registered for the treatment of several autoimmune diseases. The effect of baricitinib on the development of autoimmune blistering diseases is currently unknown.
Aims: We aimed to investigate the effect of systemic baricitinib treatment in a widely used animal model of autoantibody-induced skin blistering.
Method: Wild-type mice were treated twice daily with 10 or 25 mg/kg baricitinib by oral gavage. Experimental autoimmune skin blistering was induced by subcutaneous injection of antibodies against type VII collagen (Col7). The extent and severity of the skin lesions were monitored for 14 days. Histological changes were assessed using H&E-stained skin biopsy samples. Leukocyte accumulation in the skin was measured by flow cytometry, cytokine levels by ELISA. The in vitro effects of baricitinib on neutrophils were investigated in ROS production and human skin separation assays.
Results: Baricitinib treatment initiated concurrently with disease induction reduced both the extent and severity of skin involvement in a dose-dependent manner compared with vehicle-treated controls, with a reduction of up to 75% at the higher dose. When treatment was started after the appearance of the first skin lesions, baricitinib similarly resulted in a significant decrease in all evaluated parameters. Histological analysis demonstrated reduced dermo-epidermal separation in the treated group. Baricitinib therapy also led to decreased immune cell infiltration and lower levels of inflammatory mediators in the skin. Furthermore, baricitinib inhibited superoxide production by neutrophils in a dose-dependent manner.
Conclusion: Systemic baricitinib therapy inhibits the development of anti-Col7-induced skin blistering. This may be through its suppressive effects on inflammatory cell infiltration in the skin. Our results raise the possibility of the therapeutic use of baricitinib in autoimmune skin blistering diseases.
Funded by the Hungarian National Research, Development and Innovation Office (KKP-129954 and TKP2021-EGA-29) and the HUN-REN Hungarian Research Network (0207007).