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Gastroenterology. 2007 Nov;133(5):1522-33. Epub 2007 Aug 2.

TIM-4 expressed by mucosal dendritic cells plays a critical role in food antigen-specific Th2 differentiation and intestinal allergy.

Author information

1
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. yangp@mcmaster.ca

Abstract

BACKGROUND & AIMS:

Food allergy accounts for significant morbidity. The etiology and immune mechanisms of food allergy, however, have remained poorly understood. In this study, we aimed to determine the role of T-cell immunoglobulin-domain and mucin-domain (TIM)-4, a recently identified member of cell surface molecules, in the pathogenesis of intestinal allergy in a murine model.

METHODS:

We report that TIM-4 as well as costimulatory molecules were up-regulated in intestinal mucosal dendritic cells by in vitro or in vivo exposure to Staphylococcus enterotoxin B (SEB). SEB-conditioned intestinal dendritic cells loaded with a food macromolecule ovalbumin (OVA) induced potent OVA-specific T-helper (Th)2 lymphocyte responses in vitro and such Th2 responses were inhibited completely by TIM-4 blockade.

RESULTS:

In vivo exposure to both SEB and OVA resulted in OVA-specific Th2 differentiation and intestinal allergic responses including increased serum immunoglobulin E and Th2 cytokine levels, activation of OVA-specific Th2 cells detected both ex vivo and in situ, and mast cell degranulation. Of importance, in vivo abrogation of TIM-4 or its cognate ligand TIM-1 by using a polyclonal antibody remarkably dampened Th2 differentiation and intestinal allergy.

CONCLUSIONS:

Our study thus identifies TIM-4 as a novel molecule critically required for the development of intestinal allergy.

Comment in

PMID:
17915221
DOI:
10.1053/j.gastro.2007.08.006
[Indexed for MEDLINE]

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