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Submitted to: Nature Education
Publication Type: Review Article Publication Acceptance Date: 11/30/2011 Publication Date: 3/1/2015 Citation: Mattison, C.P. 2015. Preventing Food Allergies by Tricking Dendritic Cells. Nature Education. 8(3):10. Interpretive Summary: Food allergies are adverse responses to components (usually proteins) within the foods we eat, which result in a self-damaging response from our immune system. A multitude of cellular and molecular components are involved in the decision to tolerate or respond to foreign molecules passing through the digestive tract. Food processing is known to alter the allergenic properties of food allergens, and in some cases, processing induced modifications can act to reduce the ability of food components to act as allergens. Characterization of food processing modifications that alter food allergen properties could be used to make foods safer for those with food allergies. This article provides a review of research demonstrating that activation of a specific sugar-binding signaling pathway (the SIGNR1 pathway) in the gastrointestinal tract can induce oral tolerance to food allergens. Researchers have used an allergenic beef protein (BSA) as a model, and when modified with long sugar chains, the modified BSA was shown to trigger tolerance through expression of immunosuppressive signaling molecules and regulatory cells. This work indicates that we may be able to modify foods to recruit our own signaling networks and “teach” our immune system to ignore food allergens, thereby, preventing allergic reactions. Future research testing sugar-modified food allergens could identify potentially new therapies or processing methods that could reduce or eliminate allergens from foods. Technical Abstract: Food allergies are adverse responses to components (usually proteins) within the foods we eat, which result in a self-damaging response from our immune system. A myriad of cellular and molecular components are involved in the decision to tolerate or respond to foreign molecules that pass through the digestive tract. This article provides a review of research using a mouse model to demonstrate that activation of a C-type lectin receptor (CLR) pathway can induce oral tolerance to a model food allergen, bovine serum albumin (BSA). BSA chemically modified with long chains of mannose residues (mannosylated-BSA) to simulate bacterial glycoproteins, but not unmodified BSA; was able to prevent severe allergic reactions and lead to quantifiable differences in vascular permeability, histamine levels, and IgE levels. The mannosylated-BSA was specifically recognized by the specific-intercellular adhesion molecule-3 grabbing non-integrin related gene 1 (SIGNR1) protein, a CLR on dendritic cells. Binding and endocytosis of the mannosylated-BSA by SIGNR1 expressing dendritic cells lead to expression of IL-10 and the induction of Tr1-like cells. The Tr1-like cells expressed IL-10 and TFN-', and when transferred to sensitive mice, they were able to transmit tolerance to BSA in sensitive mice. This study indicates that some signaling networks can be recruited to induce oral tolerance to food allergens. Integration of this research with other findings from the field, suggests that future research testing sugar modified food allergens could identify potentially new therapies or processing methods that could reduce or eliminate allergens from foods. |
