Focus on Interferon Signature in Cutaneous Lupus Erythematosus: Novel Therapies From Better Understanding of the Pathogenesis

TL;DR

This review explores how interferon contributes to cutaneous lupus and highlights new therapies targeting this pathway to improve treatment.

Contribution

The paper provides a systematic analysis of the IFN-CLE axis and novel therapeutic strategies targeting interferon signaling.

Findings

Interferon-stimulated genes are highly expressed in CLE lesions, indicating a strong IFN signature.

Targeting plasmacytoid dendritic cells or IFN signaling shows therapeutic potential in CLE.

IFN-focused strategies may offer precision immunomodulation for better CLE management.

Abstract

Cutaneous lupus erythematosus (CLE), a common clinical manifestation of lupus erythematosus (LE), significantly compromises patients’ quality of life and social functioning due to its relatively high prevalence. While the exact pathogenesis of CLE remains incompletely understood, accumulating evidence highlights the pivotal role of interferon (IFN) as a central mediator in disease initiation and progression. Stromal cells and infiltrating immune cells within CLE lesions demonstrate elevated expression of IFN‐stimulated genes (ISGs), establishing a characteristic IFN signature. IFN orchestrates multiple pathological processes, including chemokine‐mediated immune cell recruitment, cutaneous inflammation cascade, and tissue fibrosis. This review systematically examines the IFN‐CLE axis through an integrated analysis of in vitro and in vivo experimental data. Emerging clinical trials reveal therapeutic promise in strategies targeting plasmacytoid dendritic cells (pDCs), neutralizing IFN signaling, or blocking downstream pathways. Given the current limitations in CLE management, IFN‐focused strategies may offer innovative solutions to address unmet clinical needs through precision immunomodulation.

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