An oral lichen planus–like mouse model driven by IFN-γ signaling and cytotoxic CD8+ T cells

TL;DR

A new mouse model mimics oral lichen planus, helping researchers study its causes and test treatments.

Contribution

The development of an OLP-like mouse model driven by IFN-γ and CD8+ T cells, with validated immunopathological and transcriptomic features.

Findings

The model shows CD8+ T cell infiltration and basal cell damage similar to human OLP.

IFN-γ signaling is critical for the OLP phenotype and disease progression.

JAK inhibitors reduced disease burden in the model.

Abstract

Oral lichen planus (OLP) is a recalcitrant inflammatory disease with potential for malignant transformation, involving a cytotoxic CD8+ T cell–mediated basal keratinocyte apoptosis. However, it lacks an appropriate mouse model for study. Here we developed an OLP-like mouse model using topical oxazolone to induce a delayed-type hypersensitivity-mediated oral lichenoid reaction. Histological and ultrastructural analysis confirmed hallmark pathological features of OLP, including band-like CD8+ T cell infiltration and basal cell damage as well as the presence of Civatte bodies. Comparative transcriptomic analysis revealed significant similarity between RNA-Seq profiles of the mouse model and human OLP lesions, highlighting shared upregulated genes and enriched pathways, particularly those related to IFN-γ signaling and cytotoxic T cell activity. Functional studies demonstrated that the OLP phenotype depended on IFN-γ, with local priming by IFN-γ intensifying the disease through upregulation of major histocompatibility complex class I. Additionally, the absence of Langerhans cells exacerbated disease severity in vivo. Therapeutic evaluation showed that the JAK inhibitors baricitinib and ruxolitinib effectively reduced disease burden and provided mechanistic insights. In conclusion, this OLP-like mouse model recapitulates key immunopathological and transcriptomic features of human OLP, offering a robust platform for dissecting disease mechanisms and evaluating novel therapeutic strategies.

A novel mouse model replicates oral lichen planus, facilitating the study of disease mechanisms and potential therapeutic strategies.

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