Low IL-13Ra1 Expression on Mast Cells Tunes Them Unresponsive to IL-13

Abstract

Abstract 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-13Ra1 mRNA. Consequently, IL-4 responses are mediated via type I IL-4R (IL-4/IL4Ra/gC) and IL-4-induced Stat6 activation is abolished in gC deficient mast cells. Type II IL-4R deficiency (IL-13Ra1 KO) has no effect on IL-4-induced Stat6 activation. In basophils, both IL-4 and IL-13 induce Stat6 activation in WT and gC 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-13Ra1 expression likely explains their unresponsiveness to IL-13. Supported by grants from Academy of Finland (grants: 25013080481 and 25013142041), The Competitive State Research Financing of the Expert Responsibility Area of Fimlab Laboratories (grant: X51409), Tampere University Hospital Support Foundation (grant: MK247), Tampere Tuberculosis Foundation, Nordlab Laboratories (grant: X3710-KT0011) and Orion Research Foundation.