PhD Scientific Days 2023

Molecular Sciences IV.

The effect of the JAK inhibitor tofacitinib in experimental autoimmune skin blistering

Előadó neve

Koncz, Petra

Neptun code

XXYYA2

Előadó munkahelye

Semmelweis University, Department of Physiology

Előadó telefonszáma

+36302167627

Előadó e-mail címe

konczpetra@gmail.com

Az előadás címe

The effect of the JAK inhibitor tofacitinib in experimental autoimmune skin blistering

Szerző(k) neve és munkahelye

Petra Koncz1, Nikolett Szénási1, Kata Petra Szilveszter1, Attila Mócsai1
1 Department of Physiology, Semmelweis University Faculty of Medicine, Budapest

Bemutatás módja

Szóbeli

Szekció

Molecular Sciences IV.

Language of the presentation

Hungarian

Preferred session

Molecular Sciences

Összefoglaló szövege

Introduction: Subepidermal autoimmune skin blistering diseases are characterized by autoantibody formation against components of the dermal-epidermal junction, leading to local proliferation and activation of inflammatory cells and consequent dissociation of the dermo-epidermal junction. Our previous experiments with gene-deficient mice have suggested the role of tyrosine kinase signalling pathways in the development of autoimmune skin blistering. Tofacitinib is a small molecule JAK inhibitor registered for the treatment of several autoimmune diseases. The effect of tofacitinib on the development of autoimmune blistering diseases is currently unknown.
Aims: We aimed to investigate the effect of systemic tofacitinib treatment in a widely used animal model of autoantibody-induced skin blistering.
Methods: Wild-type mice were treated twice daily with 16 or 50 mg/kg tofacitinib by oral gavage. Experimental autoimmune skin blistering was induced by subcutaneous injection of antibodies against type VII collagen (C7). The extent of the skin lesions and the appearance of erosions were then monitored for 14 days. Histological changes were assessed using H&E-stained ear and tongue sections. 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 of skin blistering disease in tofacitinib-treated mice. A dose of 50 mg/kg tofacitinib reduced symptoms by more than 70% overall, and inhibited the appearance of more severe lesions particularly effectively. Dermo-epidermal separation and blister formation was significantly reduced in tongue sections of tofacitinib-treated mice. Tofacitinib inhibited the migration of neutrophil granulocytes 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-C7 antibodies.
Conclusion: Systemic tofacitinib therapy inhibits the development of anti-C7-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 in autoimmune skin blistering diseases.
Funding: TKP2021-EGA-29; SEMTRHEUM project

University and Doctoral School

Semmelweis University, Doctoral School of Molecular Medicine

Supervisor

Attila Mócsai

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7517

Start

15:30

End

15:45

Authors (legacy)

Petra Koncz1, Nikolett Szénási1, Kata Petra Szilveszter1, Attila Mócsai1
1 Department of Physiology, Semmelweis University Faculty of Medicine, Budapest