PhD Scientific Days 2025

Poster Session II. - B: Molecular Medicine

ARHGAP25 has an anti-inflammatory role in the imiquimod-induced psoriasis mouse model

Name of the presenter

Bíró Renáta

Institute/workplace of the presenter

Semmelweis University Institute of Physiology

Authors

Renáta Bíró PhD¹, Péter Sasvári¹, Dr. Roland Csépányi-Kömi¹

1: Semmelweis University Institute of Physiology

Text of the abstract

Background: ARHGAP25 is a leukocyte-specific GTPase-activating protein that regulates immune cell functions and inflammation. Psoriasis is a common autoimmune skin disease with a complex, partly unclear pathogenesis. Due to its regulatory role, ARHGAP25 may contribute to psoriasis development.
Aims: This research project aims to investigate the role of ARHGAP25 in the pathomechanism of psoriasis.
Methods: We used Arhgap25+/+ (WT), Arhgap25-/- (KO), bone marrow chimeric (WT→WTCD45.1, KO→WTCD45.1), and reverse bone marrow chimeric (WTCD45.1→KO, WTCD45.1→WT) mouse strains. The psoriasiform inflammation on the skin was induced by daily Imiquimod (IMQ) application, and vaseline was used as control. The backs of the mice were shaved, and the progression of the inflammation was monitored for 6 days by measuring the double skin thickness and scoring the main visible symptoms of the inflammation (desquamation, induration, and erythema). On day 6, spleens were excised, measured, and lysed for leukocyte counting.
Results: IMQ treatment induced inflammation in WT and KO groups, with comparable increase in skin thikness. However, KO mice displayed more severe clinical symptoms, with significantly higher erythema scores from day 3 and increased desquamation scores on days 4 and 6. In bone marrow chimeras, the results closely mirrored our previously mentioned findings. Mice receiving KO hematopoietic cells on a WT background exhibited increased skin thickness and elevated clinical scores, indicating a stronger inflammatory response. Additionally, a significant increase in spleen size was observed in this group. In reverse chimeras no clear difference in inflammatory response has been observed. However, in contrast to the normal chimera results, splenomegaly was less severe in WTCD45.1→KO mice.
Conclusions: Previously, we found that ARHGAP25-deficiency mitigates the symptoms of autoantibody-induced arthritis. In this project, we successfully applied the IMQ-induced psoriasis model and, interestingly, observed more severe symptoms of inflammation upon ARHGAP25 deletion. This phenomenon was reproduced in bone marrow chimeras, suggesting a leukocyte-mediated explanation. However, further experiments are needed to better understand the underlying mechanisms.
Funding: EFOP-3.6.3-VEKOP-16-2017-00009, NKFIH FK_18/128376, TKP2021_EGA_24