Basic–Alimentary TractTIM-4 Expressed by Mucosal Dendritic Cells Plays a Critical Role in Food Antigen–Specific Th2 Differentiation and Intestinal Allergy
Section snippets
Mice
Balb/c and C57BL/6 mice (male, 6–8 weeks old) were purchased from the Charles River Laboratory (Wilmington, MA). DO11.10 TCR transgenic mice that recognize an OVA peptide in the context of I-Ad major histocompatibility complex class II (MHC II) molecules were purchased from the Jackson Laboratory (Bar Harbor, ME). The experiments were approved by the Animal Research Ethics Board at McMaster University.
Murine Model of Intestinal Allergy
C57BL/6 mice were sensitized intraperitoneally with SEB (10 μg/mouse), OVA (20 μg/mouse), or
Localization of TIM-4 Expression to DCs in Intestinal Mucosa
Apart from its high expression in the thymus, recent evidence has indicated that TIM-4 also is expressed by DCs located in the spleen and lymph nodes and only weakly is expressed in nonlymphoid tissues such as the lung and liver.13 To begin investigating the role of TIM-4 in the immune regulation of intestinal allergy, we first examined its expression and regulation within the jejunal intestinal mucosa by immunoconfocal microscopy. We found that jejunal mucosa of naive mice had easily
Discussion
Although the development of Th2 cells is believed to be a critical step in the immune mechanisms of food allergy, the factors and mechanisms involved in the initiation of food antigen–specific Th2 activation remain poorly understood. Recent evidence suggests that increased exposure of the mucosal immune system to both bacterial toxins and food antigens predisposes the host to food antigen sensitization and allergy.8, 9 However, little is known about the molecular mechanisms by which microbial
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Supported by funds from the Canadian Institutes of Health Research (P.–C.Y.).