title: Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis.
abstract: OBJECTIVE
  Eosinophils reside in the colonic mucosa and increase significantly during disease. Although a number of studies have suggested that eosinophils contribute to the pathogenesis of GI inflammation, the expanding scope of eosinophil-mediated activities indicate that they also regulate local immune responses and modulate tissue inflammation. We sought to define the impact of eosinophils that respond to acute phases of colitis in mice.
  
  
  METHODS
  Acute colitis was induced in mice by administration of dextran sulfate sodium, 2,4,6-trinitrobenzenesulfonic acid or oxazolone to C57BL/6J (control) or eosinophil deficient (PHIL) mice. Eosinophils were also depleted from mice using antibodies against interleukin (IL)-5 or by grafting bone marrow from PHIL mice into control mice. Colon tissues were collected and analysed by immunohistochemistry, flow cytometry and reverse transcription PCR; lipids were analysed by mass spectroscopy.
  
  
  RESULTS
  Eosinophil-deficient mice developed significantly more severe colitis, and their colon tissues contained a greater number of neutrophils, than controls. This compensatory increase in neutrophils was accompanied by increased levels of the chemokines CXCL1 and CXCL2, which attract neutrophils. Lipidomic analyses of colonic tissue from eosinophil-deficient mice identified a deficiency in the docosahexaenoic acid-derived anti-inflammatory mediator 10, 17- dihydroxydocosahexaenoic acid (diHDoHE), namely protectin D1 (PD1). Administration of an exogenous PD1-isomer (10S, 17S-DiHDoHE) reduced the severity of colitis in eosinophil-deficient mice. The PD1-isomer also attenuated neutrophil infiltration and reduced levels of tumour necrosis factor-α, IL-1β, IL-6 and inducible NO-synthase in colons of mice. Finally, in vitro assays identified a direct inhibitory effect of PD1-isomer on neutrophil transepithelial migration.
  
  
  CONCLUSIONS
  Eosinophils exert a protective effect in acute mouse colitis, via production of anti-inflammatory lipid mediators.
authors.affiliation: Section of Pediatric Gastroenterology, Hepatology and Nutrition, Gastrointestinal Eosinophilic Diseases Program, Department of Pediatrics; Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado, USA University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Joanne C
authors.initials: JC
authors.lastname: Masterson
authors.affiliation: Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado, USA University of Colorado School of Medicine, Aurora, Colorado, USA Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Eóin N
authors.initials: EN
authors.lastname: McNamee
authors.affiliation: Section of Pediatric Gastroenterology, Hepatology and Nutrition, Gastrointestinal Eosinophilic Diseases Program, Department of Pediatrics; Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado, USA University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Fillon
authors.affiliation: Section of Pediatric Gastroenterology, Hepatology and Nutrition, Gastrointestinal Eosinophilic Diseases Program, Department of Pediatrics; Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado, USA University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Hosford
authors.affiliation: Section of Pediatric Gastroenterology, Hepatology and Nutrition, Gastrointestinal Eosinophilic Diseases Program, Department of Pediatrics; Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado, USA University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Harris
authors.affiliation: Section of Pediatric Gastroenterology, Hepatology and Nutrition, Gastrointestinal Eosinophilic Diseases Program, Department of Pediatrics; Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado, USA University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Shahan D
authors.initials: SD
authors.lastname: Fernando
authors.affiliation: University of Colorado School of Medicine, Aurora, Colorado, USA Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Jedlicka
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Iwamoto
authors.affiliation: Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Scottsdale, Arizona, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jacobsen
authors.affiliation: Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Scottsdale, Arizona, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Protheroe
authors.affiliation: Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado, USA University of Colorado School of Medicine, Aurora, Colorado, USA Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Holger K
authors.initials: HK
authors.lastname: Eltzschig
authors.affiliation: Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado, USA University of Colorado School of Medicine, Aurora, Colorado, USA Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Colgan
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Scottsdale, Arizona, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Section of Pediatric Gastroenterology, Hepatology and Nutrition, Gastrointestinal Eosinophilic Diseases Program, Department of Pediatrics; Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado, USA University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Glenn T
authors.initials: GT
authors.lastname: Furuta
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003092:Colitis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000473:pathology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000893:Anti-Inflammatory Agents
keywords: IBD BASIC RESEARCH; IMMUNOREGULATION; INFLAMMATION; LIPID MEDIATORS; MUCOSAL IMMUNOLOGY