Intratracheal IL-13 induces eosinophilic esophagitis by an IL-5, eotaxin-1, and STAT6-dependent mechanism.
OBJECTIVE
Eosinophil infiltration into the esophagus occurs in a wide range of diseases; however, the underlying pathophysiologic mechanisms involved are largely unknown. We have previously reported that simultaneous delivery of allergen to the lung and gastrointestinal tract induces experimental eosinophilic esophagitis (EE). We aimed to determine whether delivery of a Th2 cytokine (interleukin [IL]-13) to the lung was sufficient for induction of EE.


METHODS
IL-13 was delivered intratracheally to wild-type, signal transducer and activator of transcription (STAT) 6, eotaxin-1, or IL-5-deficient mice. Eosinophil levels and 5'-bromodeoxyuridine (BrdU) incorporation were examined by immunohistochemical staining.


RESULTS
Intratracheal delivery of IL-13 induced dose-dependent eosinophil accumulation in the esophagus (but not the stomach). In addition, intratracheal IL-13 induced esophageal epithelial hyperplasia. The ability of IL-13 to induce EE was abolished in STAT6-deficient mice. IL-13-induced EE was nearly completely ablated in IL-5-deficient mice (37.3 +/- 11.6 vs. 3.3 +/- 3.2 eosinophils/mm(2) in wild-type and IL-5-deficient mice, respectively). Additionally, IL-13-induced EE was significantly diminished in eotaxin-1-deficient mice (48.7 +/- 10.3 vs. 14.1 +/- 12.5 eosinophils/mm(2) in wild-type and eotaxin-1-deficient mice, respectively).


CONCLUSIONS
IL-13 delivery to the lung induces EE by an IL-5, eotaxin-1, and STAT6-dependent mechanism. These results further establish an intimate connection between respiratory and esophageal inflammation.
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Anil
A
Mishra
Marc E
ME
Rothenberg
D000818:Animals; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004802:Eosinophilia / Q000139:chemically induced* / Q000473:pathology; D004941:Esophagitis / Q000139:chemically induced* / Q000473:pathology; D004947:Esophagus / Q000473:pathology; D006965:Hyperplasia; D018793:Interleukin-13 / Q000008:administration & dosage*; D015848:Interleukin-5 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009994:Osmolar Concentration; D050800:STAT6 Transcription Factor; D014132:Trachea; D015534:Trans-Activators / Q000378:metabolism*
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D018793:Interleukin-13; D015848:Interleukin-5; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators