title: Interplay of adaptive th2 immunity with eotaxin-3/c-C chemokine receptor 3 in eosinophilic esophagitis.
abstract: BACKGROUND
  Pediatric eosinophilic esophagitis (EE) is a recently described disorder associated with atopy. Although studies of esophageal tissue suggest that Th2 cytokines and eotaxin-3 may be crucial in disease pathogenesis, little is known about the systemic immunological phenotypes of children with EE.
  
  
  OBJECTIVE
  To define the phenotypes of peripheral blood eosinophils and lymphocytes in EE and to examine for correlations between these parameters and tissue eosinophil numbers and disease severity.
  
  
  METHODS
  Blood was collected from children with EE, atopic control children without EE, and nonatopic control children without EE. Flow cytometry was used to measure eosinophil expression of chemokine receptor 3 (CCR3) and interleukin-5 receptor-alpha (IL-5Ralpha), and intracellular lymphocyte expression of IL-4, IL-5, IL-13, interferon-gamma, and tumor necrosis factor-alpha. Eosinophil numbers and eotaxin-3 mRNA levels were quantitated in esophageal biopsy specimens.
  
  
  RESULTS
  Compared with nonatopic control children, EE patients with active disease had increased peripheral blood eosinophil percentages, mean channel of fluorescence (MCF) of CCR3 on eosinophils, and percentage of CD4+ T cells expressing IL-5. Notably, these parameters positively correlated with esophageal eosinophil numbers. Eotaxin-3 tissue expression positively correlated with esophageal eosinophil numbers and peripheral blood eosinophil CCR3 MCF. The percentage of peripheral blood eosinophils, eosinophil CCR3 MCF, and CD4+ T cell expression of IL-5 were lower in EE patients in disease remission than in patients with active disease.
  
  
  CONCLUSIONS
  Collectively, these studies demonstrate cooperation between systemic CD4+ Th2-cell-mediated immunity and an enhanced eosinophil-CCR3/eotaxin-3 pathway in EE pathogenesis. Furthermore, the imbalanced Th2 immunity and increased CCR3 expression are reversible with disease remission.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA.
authors.forename: Jennifer Z
authors.initials: JZ
authors.lastname: Bullock
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Villanueva
authors.forename: Carine
authors.initials: C
authors.lastname: Blanchard
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
authors.forename: Philip E
authors.initials: PE
authors.lastname: Putnam
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Collins
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Risma
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Akers
authors.forename: Cassie L
authors.initials: CL
authors.lastname: Kirby
authors.forename: Bridget K
authors.initials: BK
authors.lastname: Buckmeier
authors.forename: Amal H
authors.initials: AH
authors.lastname: Assa'ad
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hogan
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000954:Antigens, Surface; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000096:biosynthesis / Q000276:immunology*; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D004802:Eosinophilia / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D004941:Esophagitis / Q000276:immunology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D007111:Immunity, Cellular; D012333:RNA, Messenger / Q000096:biosynthesis; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000954:Antigens, Surface; C120429:CCL26 protein, human; C515350:CCR3 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D016207:Cytokines; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019707:Receptors, Chemokine