title: IL-10-induced gp130 expression in mouse mast cells permits IL-6 trans-signaling.
abstract: It is reported that human and mouse mast cells express the IL-27R, which consists of WSX-1 (the IL-27Rα 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-α 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.
authors.affiliation: Department of Medicine, University of Pennsylvania School of Medicine, 421 Curie Blvd., Philadelphia, PA 19104, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Traum
authors.forename: Patricia
authors.initials: P
authors.lastname: Timothee
authors.forename: Jonathan
authors.initials: J
authors.lastname: Silver
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.forename: Matthias
authors.initials: M
authors.lastname: Ernst
authors.forename: David F
authors.initials: DF
authors.lastname: LaRosa
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D016753:Interleukin-10 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D007378:Interleukins / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D016192:Resting Phase, Cell Cycle; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
chemical_list: D016207:Cytokines; C486767:Il27 protein, mouse; D015850:Interleukin-6; D007378:Interleukins; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016753:Interleukin-10; D050822:Cytokine Receptor gp130