# Genetic deletion of microsomal prostaglandin E synthase-1 promotes imiquimod-induced psoriasis in mice

## TL;DR

Deleting a specific enzyme in mice worsens psoriasis symptoms, suggesting it plays a key role in skin inflammation and immune response.

## Contribution

This study reveals that mPGES-1 deficiency exacerbates psoriasis by influencing T-cell immunity in a mouse model.

## Key findings

- mPGES-1 is the main enzyme responsible for PGE2 production in the skin.
- mPGES-1 deficiency increases IL-17A-producing γδ T cells, worsening psoriasis.
- γδ T-cell depletion reduces psoriasis symptoms in mPGES-1-deficient mice.

## Abstract

Psoriasis is a chronic inflammatory disease associated with abnormalities in the immune system. Microsomal prostaglandin E synthase-1 (mPGES-1), a terminal enzyme for prostaglandin (PG) E2 biosynthesis, is highly expressed in the skin of psoriasis patients. However, the detailed role of mPGES-1 in psoriasis remains unclear. In the present study, we aimed to investigate the role of mPGES-1 in psoriasis-like skin inflammation induced by imiquimod (IMQ), a well-established model of psoriasis.

Psoriasis was induced in mPGES-1-deficient (mPGES-1−/−) and wild-type (WT) mice by administering IMQ for 6 days. Psoriasis was evaluated based on the scores of the macroscopic symptoms, including skin scaling, thickness, and redness, and on the histological features. The skin expression of mPGES-1 was determined by real-time polymerase chain reaction and Western blotting. The impact of mPGES-1 deficiency on T-cell immunity was determined by flow cytometry and γδ T-cell depletion in vivo with anti-T-cell receptor (TCR) γδ antibody.

The inflamed skin of mPGES-1−/− mice showed severe symptoms after the administration of IMQ. Histological analysis further showed significant exacerbation of psoriasis in mPGES-1−/− mice. In WT mice, the mPGES-1 expression was highly induced at both mRNA and protein levels in the skin, and PGE2 increased significantly after IMQ administration, while the PGE2 production was largely abolished in mPGES-1−/− mice. These data indicate that mPGES-1 is the main enzyme responsible for PGE2 production in the skin. Furthermore, the lack of mPGES-1 increased the numbers of IL-17A-producing γδ T cells in the skin with IMQ-induced psoriasis, and γδ T-cell depletion resulted in a reduction of the facilitated psoriasis symptoms under the condition of mPGES-1 deficiency.

Our study results demonstrate that mPGES-1 is the main enzyme responsible for skin PGE2 production, and that mPGES-1 deficiency facilitates the development of psoriasis by affecting the development of T-cell-mediated immunity. Therefore, mPGES-1 might impact both skin inflammation and T-cell-mediated immunity associated with psoriasis.

The online version contains supplementary material available at 10.1186/s41232-025-00385-2.