Single cell transcriptomics of human psoriasis and epidermal specific Ube2l3 deficient mice highlight CXCL16/CXCR6 involvement in psoriasis development

Xue-Yan Chen ¹, Li-Ran Ye ¹, Ni-Chang Fu ¹

⁰Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Nature Communications +

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October 13, 2025

View abstract on PubMed

Summary

UBE2L3 acts as a protective biomarker in psoriasis, suppressing IL-17A production in skin cells. Its reduction activates inflammatory pathways, contributing to psoriatic lesions.

Area Of Science

Immunology
Dermatology
Molecular Biology

Background

Psoriasis is a chronic immune-mediated inflammatory disease.
Keratinocytes, dendritic cells, and T cells are key players in its pathogenesis.
UBE2L3 is investigated as a potential protective biomarker.

Purpose Of The Study

To investigate the role of UBE2L3 in psoriasis pathogenesis.
To identify similarities in IL-17A signaling between human and mouse psoriatic skin.
To elucidate the CXCL16/CXCR6 signaling pathway in psoriasis.

Main Methods

Comparative analysis of psoriatic skin from humans and Ube2l3 conditional knockout mice.
Investigation of IL-17A signaling pathways.
Analysis of chemokine (CXCL16) and receptor (CXCR6) interactions.
Examination of STAT3 signaling in keratinocytes.

Main Results

Identified IL-17A signaling similarity in the epidermis of human and mouse psoriatic skin.
Demonstrated that UBE2L3 reduction in keratinocytes activates IL-1β and promotes CXCL16 expression via STAT3.
Showed that CXCL16 attracts specific T cell subsets (γδT17 or CD8+) to produce IL-17A, forming a positive feedback loop.

Conclusions

UBE2L3 acts as a keratinocyte-intrinsic suppressor of epidermal IL-17 production.
The CXCL16/CXCR6 signaling pathway is crucial in mediating IL-17A production by T cells in psoriasis.
UBE2L3 may serve as a therapeutic target for psoriasis.