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Published on: April 14, 2010
IL-4Rα-STAT6 signaling amplifies IL-1Ra production in ABCB5+ dermal mesenchymal stem cell-macrophage crosstalk
Karmveer Singh1, Brian J Wilson2, Ana Maria Waaga-Gasser3
1Department of Dermatology and Allergic Diseases, Ulm University, N27, Albert-Einstein-Allee 23, Ulm, 89081, Germany.
Abstract:
ABCB5+ dermal mesenchymal stem cells (DMSCs) regulate macrophage activation via interleukin-1 receptor antagonist (IL-1Ra), but upstream control mechanisms remain unclear. Here, we define a dual-signal model integrating inflammatory and type 2 cytokine pathways. IFNγ/LPS priming initiates IL-1Ra expression, while IL-4 signaling through IL-4Rα amplifies this response via STAT6 in both ABCB5+ DMSCs and macrophages. In coculture, ABCB5+ DMSCs drive macrophage polarization toward a CD206+/CD163+ phenotype with enrichment of CD163-expressing subsets. IL-4Rα blockade with dupilumab inhibits STAT6 activation, suppresses IL-1Ra amplification, and attenuates expansion of this IL-4Rα-dependent macrophage population. Collectively, these findings identify IL-4/IL-4Rα/STAT6 signaling as a conserved amplifier of IL-1Ra-mediated stromal-immune crosstalk.
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