title: Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis.
abstract: Eosinophilic esophagitis (EE) is an emerging disorder with a poorly understood pathogenesis. In order to define disease mechanisms, we took an empirical approach analyzing esophageal tissue by a genome-wide microarray expression analysis. EE patients had a striking transcript signature involving 1% of the human genome that was remarkably conserved across sex, age, and allergic status and was distinct from that associated with non-EE chronic esophagitis. Notably, the gene encoding the eosinophil-specific chemoattractant eotaxin-3 (also known as CCL26) was the most highly induced gene in EE patients compared with its expression level in healthy individuals. Esophageal eotaxin-3 mRNA and protein levels strongly correlated with tissue eosinophilia and mastocytosis. Furthermore, a single-nucleotide polymorphism in the human eotaxin-3 gene was associated with disease susceptibility. Finally, mice deficient in the eotaxin receptor (also known as CCR3) were protected from experimental EE. These results implicate eotaxin-3 as a critical effector molecule for EE and provide insight into disease pathogenesis.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
authors.forename: Carine
authors.initials: C
authors.lastname: Blanchard
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Keith F
authors.initials: KF
authors.lastname: Stringer
authors.forename: Anil
authors.initials: A
authors.lastname: Mishra
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Fulkerson
authors.forename: J Pablo
authors.initials: JP
authors.lastname: Abonia
authors.forename: Sean C
authors.initials: SC
authors.lastname: Jameson
authors.forename: Cassie
authors.initials: C
authors.lastname: Kirby
authors.forename: Michael R
authors.initials: MR
authors.lastname: Konikoff
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Collins
authors.forename: Mitchell B
authors.initials: MB
authors.lastname: Cohen
authors.forename: Rachel
authors.initials: R
authors.lastname: Akers
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hogan
authors.forename: Amal H
authors.initials: AH
authors.lastname: Assa'ad
authors.forename: Philip E
authors.initials: PE
authors.lastname: Putnam
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Aronow
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000818:Animals; D001706:Biopsy; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D002648:Child; D004802:Eosinophilia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004941:Esophagitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008415:Mastocytosis / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide
chemical_list: C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC