title: Macrophage migration inhibitory factor promotes eosinophil accumulation and tissue remodeling in eosinophilic esophagitis.
abstract: Macrophage migration inhibitory factor (MIF) is involved in eosinophil biology and in type 2 inflammation, contributing to allergic and helminthic diseases. We hypothesized that MIF participates in the pathogenesis of eosinophilic esophagitis (EoE), an allergic condition characterized by esophageal eosinophilic inflammation. MIF is highly expressed in esophageal mucosa of patients with EoE, compared with gastro-esophageal reflux disease and control patients, where it co-localizes predominantly with eosinophils. In vitro, recombinant MIF promotes human eosinophil chemotaxis, while MIF antagonist and CXCR4 antagonist, AMD3100, revert this effect. In a model of EoE induced by ovalbumin, Mif-deficient mice have reduced inflammation and collagen deposition compared with wild-type (WT) mice. Importantly, treatment of WT mice with anti-MIF or with AMD3100 during the challenge phase prevents accumulation of eosinophils and tissue remodeling. Conversely, recombinant MIF promoted tissue eosinophil inflammation in allergic mice. Together, these results implicate MIF in the pathogenesis of esophageal inflammation and suggest that targeting MIF might represent a novel therapy for EoE.
authors.affiliation: 1] Serviço de Gastroenterologia & Laboratório Multidisciplinar de Pesquisa, Department of Internal Medicine, Hospital Universitário, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil [2] D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
authors.forename: H S
authors.initials: HS
authors.lastname: de Souza
authors.affiliation: Serviço de Gastroenterologia & Laboratório Multidisciplinar de Pesquisa, Department of Internal Medicine, Hospital Universitário, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: C A
authors.initials: CA
authors.lastname: Tortori
authors.affiliation: Laboratório de Inflamação e Imunidade, Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Lintomen
authors.affiliation: Instituto de Ciências Biomédicas, Pólo de Xerém, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: R T
authors.initials: RT
authors.lastname: Figueiredo
authors.affiliation: Serviço de Gastroenterologia & Laboratório Multidisciplinar de Pesquisa, Department of Internal Medicine, Hospital Universitário, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Bernardazzi
authors.affiliation: Department of Medicine/Rheumatology, Yale University School of Medicine, The Anlyan Center, New Haven, CT, USA.
authors.forename: L
authors.initials: L
authors.lastname: Leng
authors.affiliation: Department of Medicine/Rheumatology, Yale University School of Medicine, The Anlyan Center, New Haven, CT, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bucala
authors.affiliation: Serviço de Gastroenterologia & Laboratório Multidisciplinar de Pesquisa, Department of Internal Medicine, Hospital Universitário, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: K
authors.initials: K
authors.lastname: Madi
authors.affiliation: Serviço de Gastroenterologia & Laboratório Multidisciplinar de Pesquisa, Department of Internal Medicine, Hospital Universitário, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Buongusto
authors.affiliation: 1] Serviço de Gastroenterologia & Laboratório Multidisciplinar de Pesquisa, Department of Internal Medicine, Hospital Universitário, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil [2] D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
authors.forename: C C S
authors.initials: CC
authors.lastname: Elia
authors.affiliation: Laboratório de Imunologia Celular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: M T L
authors.initials: MT
authors.lastname: Castelo-Branco
authors.affiliation: Laboratório de Inflamação e Imunidade, Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: M T
authors.initials: MT
authors.lastname: Bozza
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001596:Benzylamines; D000080027:Cyclams; D057765:Eosinophilic Esophagitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005260:Female; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000276:immunology*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology / Q000473:pathology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology
chemical_list: D001596:Benzylamines; C527276:CXCR4 protein, human; C514936:CXCR4 protein, mouse; D000080027:Cyclams; D006571:Heterocyclic Compounds; D008263:Macrophage Migration-Inhibitory Factors; D019718:Receptors, CXCR4; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human; C076231:Mif protein, mouse; C088327:plerixafor