کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3296003 | 1209863 | 2007 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: TIM-4 Expressed by Mucosal Dendritic Cells Plays a Critical Role in Food Antigen–Specific Th2 Differentiation and Intestinal Allergy TIM-4 Expressed by Mucosal Dendritic Cells Plays a Critical Role in Food Antigen–Specific Th2 Differentiation and Intestinal Allergy](/preview/png/3296003.png)
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.
Journal: Gastroenterology - Volume 133, Issue 5, November 2007, Pages 1522–1533