title: IL-33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells.
abstract: Eosinophils are multifunctional leukocytes involved in allergic reactions as well as adipose tissue regulation. IL-5 is required for eosinophil survival; however, the in vivo mechanisms of eosinophil regulation are not fully understood. A tg mouse model with il5 promoter-driven EGFP expression was established for detecting the IL-5-producing cells in vivo. Il5-egfp tg mice expressed high levels of EGFP in gonadal adipose tissue (GAT) cells. EGFP(+) cells in GAT were mainly group 2 innate lymphoid cells (ILCs). IL-33 preferentially expanded EGFP(+) cells and eosinophils in GAT in vivo. EGFP(+) ILCs were found to upregulate prg2 mRNA expression in GAT eosinophils. These results demonstrate that ILCs activate eosinophils in GAT. The blockage of IL-33Rα, on the other hand, did not impair EGFP(+) ILC numbers but did impair eosinophil numbers in vivo. GAT eosinophils expressed IL-33Rα and IL-33 expanded eosinophil numbers in CD90(+) cell-depleted mice. IL-33 was further observed to induce the expression of retnla and epx mRNA in eosinophils. These findings demonstrate that IL-33 directly activates eosinophils in GAT, and together with our other findings described above, our findings show that IL-33 has dual pathways via which it activates eosinophils in vivo: a direct activation pathway and a group 2 ILC-mediated pathway.
authors.affiliation: Department of Immunology, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hashiguchi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kashiwakura
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Kojima
authors.forename: Ayano
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kanno
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Kobata
mesh_terms: D000818:Animals; D047093:Eosinophil Major Basic Protein / Q000235:genetics / Q000276:immunology; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D007113:Immunity, Innate / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D000067596:Interleukin-33; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: C506535:Il33 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D000067596:Interleukin-33; D015848:Interleukin-5; D007378:Interleukins; C479219:Prg3 protein, mouse; C413576:Retnla protein, mouse; D047093:Eosinophil Major Basic Protein
keywords: Eosinophils; IL-33; IL-5; Innate lymphoid cells