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Low IL-13Rα1 Expression on Mast Cells Tunes Them Unresponsive to IL-13.
Journal of Leukocyte Biology 2023 May 25
Cytokine-mediated mast cell regulation enables precise optimization of their own pro-inflammatory cytokine production. During allergic inflammation, Interleukin(IL)-4 regulates mast cell functions, tissue-homing and proliferation, but the direct role of closely related IL-13 for mast cell activation remains unclear. Previous work has shown that mast cells are potent IL-13 producers, but here we show that mouse mast cells do not directly respond to IL-13 by Stat6 activation, as they do not express measurable amount of IL-13Rα1 mRNA. Consequently, IL-4 responses are mediated via type I IL-4R (IL-4/IL4Rα/γC) and IL-4-induced Stat6 activation is abolished in γC deficient mast cells. Type II IL-4R deficiency (IL-13Rα1 KO) has no effect on IL-4-induced Stat6 activation. In basophils, both IL-4 and IL-13 induce Stat6 activation in WT and γC deficient cells, while in type II IL-4R deficient basophils IL-4 signaling is impaired at low ligand concentration. Thus, mast cell and basophil sensitivity to IL-4/IL-13 is different and in mast cells, lack of IL-13Rα1 expression likely explains their unresponsiveness to IL-13.
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