title: IL-1β in eosinophil-mediated small intestinal homeostasis and IgA production.
abstract: Eosinophils are multifunctional leukocytes that reside in the gastrointestinal (GI) lamina propria, where their basal function remains largely unexplored. In this study, by examining mice with a selective deficiency of systemic eosinophils (by lineage ablation) or GI eosinophils (eotaxin-1/2 double deficient or CC chemokine receptor 3 deficient), we show that eosinophils support immunoglobulin A (IgA) class switching, maintain intestinal mucus secretions, affect intestinal microbial composition, and promote the development of Peyer's patches. Eosinophil-deficient mice showed reduced expression of mediators of secretory IgA production, including intestinal interleukin 1β (IL-1β), inducible nitric oxide synthase, lymphotoxin (LT) α, and LT-β, and reduced levels of retinoic acid-related orphan receptor gamma t-positive (ROR-γt(+)) innate lymphoid cells (ILCs), while maintaining normal levels of APRIL (a proliferation-inducing ligand), BAFF (B cell-activating factor of the tumor necrosis factor family), and TGF-β (transforming growth factor β). GI eosinophils expressed a relatively high level of IL-1β, and IL-1β-deficient mice manifested the altered gene expression profiles observed in eosinophil-deficient mice and decreased levels of IgA(+) cells and ROR-γt(+) ILCs. On the basis of these collective data, we propose that eosinophils are required for homeostatic intestinal immune responses including IgA production and that their affect is mediated via IL-1β in the small intestine.
authors.affiliation: 1] Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA [2] Department of Microbiology, Graduate School of Medicine, Gachon University, Incheon, Republic of Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: T
authors.initials: T
authors.lastname: Wen
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Mingler
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Caldwell
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Y H
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Chaplin
authors.affiliation: Department of Microbiology, Graduate School of Medicine, Gachon University, Incheon, Republic of Korea.
authors.forename: E H
authors.initials: EH
authors.lastname: Lee
authors.affiliation: 1] Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea [2] Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: M H
authors.initials: MH
authors.lastname: Jang
authors.affiliation: Department of Microbiology, Graduate School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: S Y
authors.initials: SY
authors.lastname: Woo
authors.affiliation: Department of Microbiology, Graduate School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Seoh
authors.affiliation: WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Miyasaka
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002452:Cell Count; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome; D015870:Gene Expression; D006706:Homeostasis; D007108:Immune Tolerance; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007421:Intestine, Small / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D008233:Lymphotoxin-alpha / Q000235:genetics; D053308:Lymphotoxin-beta / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D010581:Peyer's Patches / Q000276:immunology / Q000378:metabolism; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D053583:Interleukin-1beta; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta