PhD Scientific Days 2026

Molecular Medicine 2.

ARHGAP25 regulates hematopoietic cell-dependent inflammation in the imiquimod-induced psoriasiform dermatitis model

Name of the presenter

Bíró, Renáta

Institute/workplace of the presenter

Department of Physiology,Semmelweis University, Budapest, Hungary

Authors

Renáta Bíró¹, Péter Sasvári², Domonkos Czárán², Roland Csépányi-Kömi²
1: Department of Physiology,Semmelweis University, Budapest, Hungary
2: Department of Physiology, Semmelweis University, Budapest, Hungary

Text of the abstract

Background: ARHGAP25 is a leukocyte-specific GTPase-activating protein that plays an important role in the regulation of immune cell function and inflammatory responses. Psoriasis is a chronic immune-mediated skin disease with a complex and not yet fully understood pathogenesis. Given the regulatory role of ARHGAP25 in inflammation, it may also contribute to the development and severity of psoriatic skin inflammation.
Aims: This study aimed to investigate the role of ARHGAP25 in the pathogenesis of psoriasis using the imiquimod (IMQ)-induced psoriasiform mouse model, with particular focus on disease severity and the contribution of hematopoietic cells.
Methods: The experiments were performed using wild-type (WT), ARHGAP25-deficient (KO), and bone marrow chimeric (WT→WT, KO→WT,WT→KO, KO→KO) mice were used in our experiments. Psoriasiform inflammation was induced by daily topical IMQ treatment for 6 consecutive days, while control animals received Vaseline. Disease progression was monitored by measuring skin thickness and scoring erythema, scaling, and induration. Following the treatment period, animals were further monitored for an additional 10–11 days to assess the resolution phase. To evaluate immune cell infiltration, skin samples were collected on days 4, 6, and 10. Infiltration was analyzed by flow cytometry and hematoxylin and eosin staining, and quantitative PCR (qPCR) analyses are planned to determine the expression of inflammatory markers.
Results: IMQ treatment induced pronounced inflammation in all experimental groups. ARHGAP25-deficient mice exhibited more severe clinical symptoms compared to WT animals, reflected by increased erythema and scaling scores. These findings were partially recapitulated in bone marrow chimeric mice, suggesting that hematopoietic cells contribute to the observed phenotype. Ongoing analyses of skin-infiltrating immune cells are expected to provide further insight into the cellular mechanisms underlying these differences.
Conclusions: Our results suggest that ARHGAP25 plays an anti-inflammatory role in the IMQ-induced psoriasiform dermatitis model, at least in part through hematopoietic cell-dependent mechanisms.
Funding: FK_18 128376, TKP2021-EGA-24