PhD Scientific Days 2025

Poster Session III. - K: Theoretical and Translational Medicine

The effect of JAK inhibitors in experimental autoimmune skin blistering

Name of the presenter

Koncz Petra

Institute/workplace of the presenter

Semmelweis University, Department of Physiology

Authors

Petra Koncz¹, Kata Petra Szilveszter¹, Nikolett Szénási¹, Attila Mócsai¹

1: Department of Physiology

Text of the abstract

Introduction: Subepidermal autoimmune skin blistering diseases are characterized by autoantibody formation against components of the dermal-epidermal junction, leading to infiltration of inflammatory cells and consequent dissociation of the junction. Tofacitinib and baricitinib are small molecule JAK inhibitors registered for the treatment of several autoimmune diseases.
Aims: We aimed to investigate the effect of systemic JAK inhibitor treatment in an animal model of autoantibody-induced skin blistering.
Methods: Wild-type mice were treated twice daily with 16 or 50 mg/kg tofacitinib or 10 or 30 mg/kg baricitinib by oral gavage. Experimental autoimmune skin blistering was induced by subcutaneous injection of antibodies against type VII collagen (Col7). The skin symptoms were monitored for 14 days. Histological changes were assessed using H&E-stained sections. Immune cell infiltration and proinflammatory mediator levels in the ears were measured by flow cytometry and ELISA, respectively. The in vitro effects of tofacitinib on neutrophils were investigated in human skin separation assays and Transwell migration experiments.
Results: Macroscopic examination revealed a significant dose-dependent reduction of skin symptoms in tofacitinib-treated and in baricitinib-treated mice. Dermo-epidermal separation and blister formation was significantly reduced in tongue sections of JAK inhibitor-treated mice. Tofacitinib inhibited the migration of neutrophils observed under in vitro conditions, but did not affect the development of an inflammatory environment in vivo. Tofacitinib also did not affect human skin separation in vitro in the presence of anti-Col7 antibodies.
Conclusion: Systemic tofacitinib and baricitinib therapy inhibits the development of anti-Col7-induced skin blistering. This may be due to the inhibition of the migratory ability of neutrophils by tofacitinib. Our results raise the possibility of the therapeutic use of tofacitinib and baricitinib in autoimmune skin blistering diseases.
Funding: Funded by the Hungarian National Research, Development and Innovation Office (KKP-129954 and TKP2021-EGA-29) and the HUN-REN Hungarian Research Network (0207007).