Abstract
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.
Original language | English |
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Pages (from-to) | 187-194 |
Number of pages | 8 |
Journal | Journal of Leukocyte Biology |
Volume | 114 |
Issue number | 2 |
DOIs | |
Publication status | Published - 27 Jul 2023 |
Publication type | A1 Journal article-refereed |
Keywords
- allergy
- basophil
- cytokine
- IgE
- IL-13
- IL-13R1
- interleukin (IL)-4
- mast cell
- papain
- Stat6 phosphorylation
Publication forum classification
- Publication forum level 1
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Cell Biology