Eosinophil-derived interferon-lambda contributes to initiation of allergen-related inflammation in the intestine.
OBJECTIVE
Epithelial barrier dysfunction plays a critical role in the initiation of a number of immune diseases; the causative factors are not fully understood. The present study aimed to elucidate the mechanism by which the eosinophil-derived interferon (IFN)-lambda induced the gut epithelial barrier dysfunction.


METHODS
The duodenal biopsies were obtained from patients with or without food allergies. The eosinophils and IFNλ expression were observed by immune staining. Intestinal epithelial cell line, T84 cells, and a mouse model were employed to observe the effect of IFNλ on the epithelial barrier function and the initiation of skewed T helper (Th)2 polarization in the mouse intestine.


RESULTS
IFNλ expression was observed in over 80% human eosinophils of the subjects with or without food allergies. Exposure to microbial products, lipopolysaccharide or peptidoglycan, could induce eosinophils to release IFNλ. Exposure to IFNλ could induce intestinal epithelial barrier dysfunction via inducing the epithelial cell apoptosis. Concurrent exposure to microbial products and food antigens could induce aberrant antigen specific Th2 polarization and Th2 pattern inflammation in the intestine.


CONCLUSIONS
Eosinophils express IFNλ that can induce intestinal epithelial barrier dysfunction and promotes the initiation of the aberrant Th2 polarization in the intestine.
Clinical Experimental Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. shaohenghe@hotmail.com
Shao-Heng
SH
He
Chun-Hua
CH
Song
Zhigang
Z
Liu
Huiyun
H
Zhang
Wenjing
W
Ma
Lin-Fu
LF
Zhou
Tahrin
T
Mahmood
Ping-Chang
PC
Yang
D000485:Allergens / Q000378:metabolism*; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000378:metabolism*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D007372:Interferons / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C
D000485:Allergens; D007372:Interferons