title: Intraperitoneal influx of neutrophils in response to IL-33 is mast cell-dependent.
abstract: IL-33 is a recently discovered cytokine involved in induction of Th2 responses and functions as an alarmin. Despite numerous recent studies targeting IL-33, its role in vivo is incompletely understood. Here we investigated inflammatory responses to intraperitoneal IL-33 injections in wild-type and mast cell-deficient mice. We found that wild-type mice, but not mast cell-deficient W(sh)/W(sh) mice, respond to IL-33 treatment with neutrophil infiltration to the peritoneum, whereas other investigated cell types remained unchanged. In W(sh)/W(sh) mice, the IL-33-induced innate neutrophil response could be rescued by local reconstitution with wild-type but not with T1/ST2(-/-) mast cells, demonstrating a mast cell-dependent mechanism. Furthermore, we found this mechanism to be partially dependent on mast cell-derived TNF, as we observed reduced neutrophil infiltration in W(sh)/W(sh) mice reconstituted with TNF(-/-) bone marrow-derived mast cells compared with those reconstituted with wild-type bone marrow-derived mast cells. In agreement with our in vivo findings, we demonstrate that human neutrophils migrate toward the supernatant of IL-33-treated human mast cells. Taken together, our findings reveal that IL-33 activates mast cells in vivo to recruit neutrophils, a mechanism dependent on IL-33R expression on peritoneal mast cells. Mast cells activated in vivo by IL-33 probably play an important role in inflammatory reactions.
authors.affiliation: Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Enoksson
authors.forename: Christine
authors.initials: C
authors.lastname: Möller-Westerberg
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wicher
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
authors.forename: Karin
authors.initials: K
authors.lastname: Forsberg-Nilsson
authors.forename: Carolina
authors.initials: C
authors.lastname: Lunderius-Andersson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Nilsson
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007274:Injections, Intraperitoneal; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D010529:Peritoneal Cavity / Q000166:cytology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism
chemical_list: C079241:IL1RL1 protein, human; C506536:IL33 protein, human; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D019009:Proto-Oncogene Proteins c-kit