Low IL-13Rα1 expression on mast cells tunes them unresponsive to IL-13.

Cytokine-mediated mast cell regulation enables precise optimization of their own proinflammatory 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-13 receptor α1 (IL-4Rα1) messenger RNA. 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 knockout) has no effect on IL-4-induced Stat6 activation. In basophils, both IL-4 and IL-13 induce Stat6 activation in wild-type 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. © The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology.

Citation

Tanja Salomaa, Laura Kummola, Martín Ignacio González-Rodríguez, Lotta Hiihtola, Tero A H Järvinen, Ilkka S Junttila. Low IL-13Rα1 expression on mast cells tunes them unresponsive to IL-13. Journal of leukocyte biology. 2023 Jul 27;114(2):187-194

Mesh Tags

Substances

PMID: 37224625

search → result