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Kosasih, T.

Publications and source records attributed to Kosasih, T..

2 recordsLinked to original sources
bioRxiv2026

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

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

developmental biology↗
bioRxiv2025

Skin-derived G-CSF activates pathological granulopoiesis upon psoriasis

Psoriasis is an inflammatory skin disease initiated by environmental triggers and driven by disruption of T cell cytokine network in the cutaneous milieu. The fact that complete resolution of disease by targeting key inflammatory cytokines remains challenging indicates a contribution of other immune cells to the pathogenesis. Here, we study the role of neutrophils in psoriasis, the first-line innate immune defender that is short-lived but mobile and infiltrate into various tissues. We found that upon psoriasis induction, skin-resident endothelial cells are activated to produce G-CSF which activates emergency granulopoiesis in bone marrow and induces cutaneous infiltration and accumulation of neutrophil that are functionally overactive. Depletion of neutrophils or blockage of psoriasis-driven granulopoiesis by respective neutralizing antibodies results in reducing cutaneous neutrophil burden and mitigating psoriasis pathogenesis. This mechanism might be conserved in human psoriasis as confirmed by public RNA-seq database. Our findings uncovered and detailed the pathological crosstalk between skin and BM in psoriatic inflammation, proposing a potential therapeutic approach targeting cross-organ communication.

immunology↗