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bioRxiv · 10.64898/2026.05.10.724156

RUNX1-ETO expression in epidermal keratinocytes induces progressive skin inflammation in vivo

Date, H.·Ishikawa, M.·Nishikawa, I.·Phung, H. M.·Nguyen, N. T. K.·Sashida, G.·Osato, M.·Sada, A.
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Abstract

Basal keratinocytes in the skin are essential for epidermal homeostasis and repair; however, how intrinsic alterations in these cells contribute to inflammatory skin pathology remains poorly understood. In this study, we employed a tamoxifen-inducible mouse model to express the human RUNX1-ETO fusion gene, a well-established oncogenic driver of acute myeloid leukemia, in epidermal basal keratinocytes. RUNX1-ETO induction in keratinocytes resulted in progressive skin inflammation in vivo, accompanied by splenomegaly, epidermal hyperplasia, increased cytokine production, and alterations in epidermal stem cell composition. Inflammatory lesions were prominent in the tail, ear, and plantar epidermis, whereas hair-bearing dorsal skin remained largely unaffected. RNA-seq analysis of FACS-isolated RUNX1-ETO+ basal keratinocytes revealed global changes in gene expression, characterized by the suppression of epidermal homeostatic and metabolic programs and the activation of inflammatory signaling pathways. In particular, RUNX1-ETO expression was associated with increased TNF/NF-{kappa}B and IL-6-STAT signaling, as well as interferon-associated inflammatory pathways, together with the induction of neutrophil-attracting chemokines and epithelial inflammatory mediators. Together, these findings indicate that RUNX1-ETO-mediated transcriptional dysregulation in basal keratinocytes promotes a pro-inflammatory cellular state that drives progressive skin inflammation.

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Date, H., Ishikawa, M., Nishikawa, I., Phung, H. M., Nguyen, N. T. K., Sashida, G., Osato, M., Sada, A.. 2026-05-13. RUNX1-ETO expression in epidermal keratinocytes induces progressive skin inflammation in vivo. https://doi.org/10.64898/2026.05.10.724156

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