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bioRxiv · 10.64898/2026.02.06.704488

Inflammatory IL-1 signaling remodels epidermal stem cell compartments by suppressing Wnt activity

Phung, H. M.·Nishikawa, I.·Nguyen, N. T. K.·Yesbolatova, A. K.·Hegazy, A. M.·Kosasih, T.·Aoi, J.·Fukushima, S.·Hiroyasu, S.·Takizawa, H.·Sada, A.
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Abstract

The skin epidermis is maintained by spatially organized stem cell populations with distinct cellular dynamics; however, how inflammation affects this heterogeneity remains largely unknown. Here, we demonstrate that acute skin inflammation alters epidermal stem cell compartments through IL-1-mediated suppression of canonical Wnt signaling. Lineage tracing in inflamed mouse skin revealed that slow-cycling Dlx1+ epidermal stem cell clones persist, whereas fast-cycling Slc1a3+ clones decline through enhanced differentiation and lineage conversion, driving the reorganization of epidermal stem cell compartments. IL-1 signaling is both necessary and sufficient for this change: administration of IL-1/{beta} recapitulates these effects, while transgenic induction of the IL-1 decoy receptor preserves the balance of stem cell populations. IL-1 suppresses canonical Wnt activity in both the mouse epidermis and human keratinocytes, and Wnt ligand administration restores the fast-cycling compartment in vivo. Together, these results identify a reversible IL-1-Wnt axis that governs inflammation-induced stem cell plasticity and spatial tissue remodeling. HighlightO_LIInflammation induces reversible remodeling of epidermal stem cell compartments C_LIO_LIDistinct epidermal stem cell populations exhibit differential responses to inflammation C_LIO_LIIL-1 suppresses canonical Wnt signaling, thereby biasing fast-cycling stem cell behavior C_LIO_LIReactivation of Wnt signaling restores stem cell population balance under inflammatory conditions C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/704488v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@e430e5org.highwire.dtl.DTLVardef@1464550org.highwire.dtl.DTLVardef@70ba1borg.highwire.dtl.DTLVardef@ca502c_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Phung, H. M., Nishikawa, I., Nguyen, N. T. K., Yesbolatova, A. K., Hegazy, A. M., Kosasih, T., Aoi, J., Fukushima, S., Hiroyasu, S., Takizawa, H., Sada, A.. 2026-02-09. Inflammatory IL-1 signaling remodels epidermal stem cell compartments by suppressing Wnt activity. https://doi.org/10.64898/2026.02.06.704488

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