IL-4 regulates susceptibility to intestinal inflammation in murine food allergy

• Grant number: 09/00663-4
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: June 01, 2009
• End date: November 30, 2009
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Santana da Silva
• Grantee: João Santana da Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Allergies involve a state of immediate hypersensitivity to antigens, including food proteins.The mechanism underlying the initiation and development of allergic responses involvesIL-4 that directly induces the differentiation of committed effector Th2 lymphocytes.Although it is clear that Th2 responses play a pivotal role in the development of allergicresponses, it remains unclear which mechanisms are involved in the development of theintestinal damages observed in food allergy. Accordingly, this work aimed to study the roleof Th2/IL-4 dependent responses in the development of food allergy and intestinalpathology. C57BL/6 wild type (WT) and IL-4-/- mice were sensitized with peanut proteins,challenged with peanut seeds and followed for the development of food allergy andintestinal inflammation. Results demonstrated that exposure to peanut seeds led to weightloss in WT but not in IL-4-/- mice that preserved gut integrity with no signs of mucosalinflammation. These animals presented increased levels of IgG2a in sera, suggesting a rolefor allergic antibodies in the pathogenesis of WT animals. Most importantly, results alsoshowed that lack of IL-4 modulated gut mucosal response in food allergy throughdiminished expression of TNF-± mRNA, increased Th1 IFN-³, IL-12p40, regulatorycytokines and Foxp3, demonstrating their relevance in the control of allergic inflammatoryprocesses, especially in the intestine. Finally, this study highlighted some of the complexmechanisms involved in the pathogenesis of allergic responses to food antigens in the gut,thereby providing valuable tools for directing novel therapeutic or preventive strategies tothe control of allergic enteropathy. (AU)