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PMID: 16453027 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis.

The Journal of clinical investigation ·Vol. 116 ·No. 2 ·2006-02-00 ·Pages 536-47

Blanchard C, Wang N, Stringer KF, Mishra A, Fulkerson PC, Abonia JP, Jameson SC, Kirby C, Konikoff MR, Collins MH, Cohen MB, Akers R, Hogan SP, Assa'ad AH, Putnam PE, Aronow BJ, Rothenberg ME

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.

MeSH Terms
Animals Biopsy Chemokine CCL26 Chemokines, CC/genetics,metabolism Child Eosinophilia/genetics,metabolism,pathology Esophagitis/genetics,metabolism,pathology Female Gene Expression Profiling Gene Frequency Genotype Humans Male Mastocytosis/genetics,metabolism Oligonucleotide Array Sequence Analysis Polymorphism, Single Nucleotide
Chemicals
CCL26 protein, human Chemokine CCL26 Chemokines, CC
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Blanchard Carine
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
Stringer Keith F
Mishra Anil
Fulkerson Patricia C
Abonia J Pablo
Jameson Sean C
Kirby Cassie
Konikoff Michael R
Collins Margaret H
Cohen Mitchell B
Akers Rachel
Hogan Simon P
Assa'ad Amal H
Putnam Philip E
Aronow Bruce J
Rothenberg Marc E
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI26679
Published
2006-02-00
Pages
536-47
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1359059
Subset
IM
Grants
NIAID NIH HHS · R01 AI045898 · United States
NIDDK NIH HHS · R24 DK064403 · United States
NIAID NIH HHS · R01 AI45898 · United States
Corrections
CommentIn
PMID: 17188967
External Links
PubMed source DOI: 10.1172/JCI26679 PMC Full Text View journal details
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