Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis.
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.
Blanchard
Carine
C
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Wang
Ning
N
Stringer
Keith F
KF
Mishra
Anil
A
Fulkerson
Patricia C
PC
Abonia
J Pablo
JP
Jameson
Sean C
SC
Kirby
Cassie
C
Konikoff
Michael R
MR
Collins
Margaret H
MH
Cohen
Mitchell B
MB
Akers
Rachel
R
Hogan
Simon P
SP
Assa'ad
Amal H
AH
Putnam
Philip E
PE
Aronow
Bruce J
BJ
Rothenberg
Marc E
ME
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
C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC