title: Functional interleukin-33 receptors are expressed in early progenitor stages of allergy-related granulocytes.
abstract: Interleukin-33 (IL-33) induces T helper type 2 (Th2) cytokine production and eosinophilia independently of acquired immunity, leading to innate immunity-mediated allergic inflammation. Allergy-related innate myeloid cells such as eosinophils, basophils and mast cells express the IL-33 receptor (IL-33R), but it is still unknown how IL-33 regulates allergic inflammation involving these cells and their progenitors. Here, we revealed that the functional IL-33R was expressed on eosinophil progenitors (EoPs), basophil progenitors (BaPs) and mast cell progenitors (MCPs). In the presence of IL-33, these progenitors did not expand, but produced a high amount of Th2 and pro-inflammatory cytokines such as IL-9, IL-13, IL-1β and IL-6. The amount of cytokines produced by these progenitors was greater than that by mature cells. In vivo, IL-33 stimulated the expansion of EoPs, but it was dependent upon the elevated serum IL-5 that is presumably derived from type 2 innate lymphoid cells that express functional IL-33R. These data collectively suggest that EoPs, BaPs and MCPs are not only the sources of allergy-related granulocytes, but can also be sources of allergy-related cytokines in IL-33-induced inflammation. Because such progenitors can differentiate into mature granulocytes at the site of inflammation, they are potential therapeutic targets in IL-33-related allergic diseases.
authors: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Higashi-Ku, Fukuoka, Japan.
authors: Hirofumi
authors: H
authors: Tsuzuki
authors: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Higashi-Ku, Fukuoka, Japan.
authors: Yojiro
authors: Y
authors: Arinobu
authors: Clinical Education Centre, Kyushu University Hospital, Higashi-Ku, Fukuoka, Japan.
authors: Kohta
authors: K
authors: Miyawaki
authors: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Higashi-Ku, Fukuoka, Japan.
authors: Ayako
authors: A
authors: Takaki
authors: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Higashi-Ku, Fukuoka, Japan.
authors: Shun-Ichiro
authors: SI
authors: Ota
authors: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Higashi-Ku, Fukuoka, Japan.
authors: Yuri
authors: Y
authors: Ota
authors: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Higashi-Ku, Fukuoka, Japan.
authors: Hiroki
authors: H
authors: Mitoma
authors: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Higashi-Ku, Fukuoka, Japan.
authors: Mitsuteru
authors: M
authors: Akahoshi
authors: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Higashi-Ku, Fukuoka, Japan.
authors: Yasuo
authors: Y
authors: Mori
authors: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Higashi-Ku, Fukuoka, Japan.
authors: Hiromi
authors: H
authors: Iwasaki
authors: Clinical Education Centre, Kyushu University Hospital, Higashi-Ku, Fukuoka, Japan.
authors: Hiroaki
authors: H
authors: Niiro
authors: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Higashi-Ku, Fukuoka, Japan.
authors: Hiroshi
authors: H
authors: Tsukamoto
authors: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Higashi-Ku, Fukuoka, Japan.
authors: Koichi
authors: K
authors: Akashi
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D042381:Granulocyte Precursor Cells / Q000276:immunology*; D006098:Granulocytes / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology*; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33 / Q000276:immunology*; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018123:Receptors, Interleukin / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D018836:Inflammation Mediators; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D015848:Interleukin-5; D018123:Receptors, Interleukin
keywords: basophils; cytokines; eosinophils; haematopoiesis; mast cells