TIM-4 Expressed by Mucosal Dendritic Cells Plays a Critical Role in Food Antigen-Specific Th2 Differentiation and Intestinal Allergy
2007 (English)In: Gastroenterology, ISSN 0016-5085, Vol. 133, no 5, 1522-1533 p.Article in journal (Refereed) Published
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.
IdentifiersURN: urn:nbn:se:liu:diva-48100DOI: 10.1053/j.gastro.2007.08.006OAI: oai:DiVA.org:liu-48100DiVA: diva2:268996