title: IL-33-induced hematopoietic stem and progenitor cell mobilization depends upon CCR2.
abstract: IL-33 has been implicated in the pathogenesis of asthma, atopic allergy, anaphylaxis, and other inflammatory diseases by promoting the production of proinflammatory cytokines and chemokines or Th2 immune responses. In this study, we analyzed the in vivo effect of IL-33 administration. IL-33 markedly promoted myelopoiesis in the bone marrow and myeloid cell emigration. Concomitantly, IL-33 induced hematopoietic stem and progenitor cell (HSPC) mobilization and extramedullary hematopoiesis. HSPC mobilization was mediated mainly through increased levels of CCL7 produced by vascular endothelial cells in response to IL-33. In vivo treatment of IL-33 rapidly induced phosphorylation of ERK, JNK, and p38, and inhibition of these signaling molecules completely blocked the production of CCL7 induced by IL-33. Consistently, inhibitor of CCR2 markedly reduced IL-33-mediated HSPC mobilization in vivo and migration of HSPCs in response to CCL7 in vitro. IL-33-mobilized HSPCs were capable of homing to, and of long-term reconstitution in, the bone marrow of irradiated recipients. Immune cells derived from these recipients had normal antifungal activity. The ability of IL-33 to promote migration of HSPCs and myeloid cells into the periphery and to regulate their antifungal activity represents a previously unrecognized role of IL-33 in innate immunity. These properties of IL-33 have clinical implications in hematopoietic stem cell transplantation.
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea 682-714;
authors.forename: Juyang
authors.initials: J
authors.lastname: Kim
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea 682-714;
authors.forename: Wonyoung
authors.initials: W
authors.lastname: Kim
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan, Korea 680-749;
authors.forename: Hongnga T
authors.initials: HT
authors.lastname: Le
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan, Korea 680-749;
authors.forename: U J
authors.initials: UJ
authors.lastname: Moon
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan, Korea 680-749;
authors.forename: Vuvi G
authors.initials: VG
authors.lastname: Tran
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan, Korea 680-749;
authors.forename: Hyun J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan, Korea 680-749;
authors.forename: Soyeon
authors.initials: S
authors.lastname: Jung
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan, Korea 680-749;
authors.forename: Quang-Tam
authors.initials: QT
authors.lastname: Nguyen
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan, Korea 680-749;
authors.forename: Byung-Sam
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea 682-714; and.
authors.forename: Jae-Bum
authors.initials: JB
authors.lastname: Jun
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea 682-714; Department of Surgery, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea 682-714 bkwon@mail.ulsan.ac.kr hrcho@uuh.ulsan.kr.
authors.forename: Hong R
authors.initials: HR
authors.lastname: Cho
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea 682-714; School of Biological Sciences, University of Ulsan, Ulsan, Korea 680-749; bkwon@mail.ulsan.ac.kr hrcho@uuh.ulsan.kr.
authors.forename: Byungsuk
authors.initials: B
authors.lastname: Kwon
mesh_terms: D000818:Animals; D064592:Autografts; D016026:Bone Marrow Transplantation; D054410:Chemokine CCL7 / Q000235:genetics / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000276:immunology; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology*; D038042:Myelopoiesis / Q000187:drug effects / Q000276:immunology*; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology*
chemical_list: C515451:Ccl7 protein, mouse; C515335:Ccr2 protein, mouse; D054410:Chemokine CCL7; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D054390:Receptors, CCR2; D048049:Extracellular Signal-Regulated MAP Kinases