The Exonuclease Trex2 Shapes Psoriatic Phenotype

Area of Science:

• Dermatology
• Molecular Biology
• Immunology

Background:

• Trex2 is a keratinocyte-specific exonuclease crucial for skin homeostasis after DNA damage.
• Psoriasis is a chronic, inflammatory skin condition characterized by hyperproliferation.

Purpose of the Study:

• To investigate the role of Trex2 in the pathogenesis of psoriasis.
• To determine the effect of Trex2 deficiency on psoriasis-like skin inflammation.

Main Methods:

• Analysis of Trex2 expression in human and mouse models of psoriasis.
• Utilizing Trex2 knockout mice treated with imiquimod (IMQ) or IL-23.
• Transcriptome analysis to identify gene expression changes in Trex2-deficient keratinocytes.

Main Results:

• Trex2 expression is significantly upregulated in psoriatic skin and in IMQ/IL-23 induced mouse models.
• Trex2 deficiency attenuated IMQ-induced skin inflammation and IL-23-induced ear swelling.
• Loss of Trex2 altered immune response and skin differentiation gene expression, and reduced keratinocyte apoptosis.

Conclusions:

• Trex2 is a critical factor in psoriasis pathogenesis.
• Trex2 promotes keratinocyte apoptosis and enucleation, influencing skin immune responses.
• Targeting Trex2 may offer a therapeutic strategy for psoriasis.