IL-5 promotes eosinophil trafficking to the esophagus.
Eosinophil infiltration into the esophagus occurs in a wide range of diseases; however, the underlying pathophysiological mechanisms involved are largely unknown. We now report that the Th2 cytokine, IL-5, is necessary and sufficient for the induction of eosinophil trafficking to the esophagus. We show that transgenic mice overexpressing IL-5 under the control of a T cell (CD2) or a small intestinal enterocyte (fatty acid-binding protein) promoter have markedly increased eosinophil numbers in the esophagus. For example, esophageal eosinophil levels are 1.9 +/- 0.9 and 121 +/- 14 eosinophils/mm(2) in wild-type and CD2-IL-5-transgenic mice, respectively. Consistent with this effect being mediated by a systemic mechanism, pharmacological administration of IL-5 via a miniosmotic pump in the peritoneal cavity resulted in blood and esophageal eosinophilia. To examine the role of IL-5 in oral Ag-induced esophageal eosinophilia, eosinophilic esophagitis was induced by allergen exposure in IL-5-deficient and wild-type mice. Importantly, IL-5-deficient mice were resistant to eosinophilic esophagitis. Finally, we examined the role of eotaxin when IL-5 was overproduced in vivo. Esophageal eosinophil levels in CD2-IL-5-transgenic mice were found to decrease 15-fold in the absence of the eotaxin gene; however, esophageal eosinophil numbers in eotaxin-deficient IL-5-transgenic mice still remained higher than wild-type mice. In conclusion, these studies demonstrate a central role for IL-5 in inducing eosinophil trafficking to the esophagus.
Mishra
Anil
A
Division of Allergy and Immunology, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Hogan
Simon P
SP
Brandt
Eric B
EB
Rothenberg
Marc E
ME
D000284:Administration, Oral; D000818:Animals; D018801:CD2 Antigens / Q000235:genetics; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000235:genetics / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004802:Eosinophilia / Q000276:immunology* / Q000473:pathology; D004804:Eosinophils / Q000276:immunology*; D004941:Esophagitis / Q000276:immunology* / Q000473:pathology; D004947:Esophagus / Q000276:immunology; D015848:Interleukin-5 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007421:Intestine, Small / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011401:Promoter Regions, Genetic
D018801:CD2 Antigens; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D015848:Interleukin-5; D010047:Ovalbumin