Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis by Blanchard Carine, 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 in The Journal of clinical investigation (2006). PubMed

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.

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