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TIM-4 Expressed by Mucosal Dendritic Cells Plays a Critical Role in Food Antigen-Specific Th2 Differentiation and Intestinal Allergy
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ont., Canada.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ont., Canada.
Department of Medicine, Division of Clinical Immunology, Mount Sinai School of Medicine, New York, NY, United States.
Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Surgery UHL.
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2007 (English)In: Gastroenterology, ISSN 0016-5085, Vol. 133, no 5, 1522-1533 p.Article in journal (Refereed) Published
Abstract [en]

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. © 2007 AGA Institute.

Place, publisher, year, edition, pages
2007. Vol. 133, no 5, 1522-1533 p.
National Category
Natural Sciences
URN: urn:nbn:se:liu:diva-48100DOI: 10.1053/j.gastro.2007.08.006OAI: diva2:268996
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2010-05-24

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Söderholm, Johan D
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Surgery Faculty of Health SciencesDepartment of Surgery UHL
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