IL-10-induced gp130 expression in mouse mast cells permits IL-6 trans-signaling

It is reported that human and mouse mast cells express the IL-27R, which consists of WSX-1 (the IL-27R alpha subunit) and the signal-transducing subunit gp130. Although it has been proposed that IL-27 may negatively regulate mast cell-dependent, immediate hypersensitivity responses directly, this has yet to be examined specifically. We found that mouse BMMC and primary peritoneal mast cells are unresponsive to IL-27. Consistent with this, gp130 protein in resting BMMC was not on the cell surface to a measurable degree but was found intracellularly, and data are consistent with incompletely processed N-linked glycosylation. Furthermore, BMMC constitutively expressed SOCS3, a major negative regulator of gp130 signaling. However, BMMC stimulation with IL-10 and consequential STAT3 activation increased gp130 expression, which resulted in a functional gp130 receptor on the BMMC cell surface. IL-10 has not been previously shown to regulate gp130 expression, which on the BMMC surface, permitted IL-6 trans-signaling, found to increase survival under limiting conditions and enhance IL-13 and TNF-gamma secretion. This study identifies factors that regulate mouse mast cell gp130 expression and signaling and makes conspicuous the limitations of using cultured mouse mast cells to study the effects of the IL-6/IL-12 cytokine family on mast cell biology. J. Leukoc. Biol. 91: 427-435; 2012.