title: IL-4 regulates susceptibility to intestinal inflammation in murine food allergy.
abstract: Allergies involve a state of immediate hypersensitivity to antigens, including food proteins. The mechanism underlying the initiation and development of allergic responses involves IL-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 allergic responses, it remains unclear which mechanisms are involved in the development of the intestinal damages observed in food allergy. Accordingly, this work aimed to study the role of Th2/IL-4-dependent responses in the development of food allergy and intestinal pathology. 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 and intestinal inflammation. Results demonstrated that exposure to peanut seeds led to weight loss in WT but not in IL-4-/- mice that preserved gut integrity with no signs of mucosal inflammation. These animals presented increased levels of IgG2a in sera, suggesting a role for allergic antibodies in the pathogenesis of WT animals. Most importantly, results also showed that lack of IL-4 modulated gut mucosal response in food allergy through diminished expression of TNF-alpha mRNA, increased Th1 IFN-gamma, IL-12p40, regulatory cytokines, and Foxp3, demonstrating their relevance in the control of allergic inflammatory processes, especially in the intestine. Finally, this study highlighted some of the complex mechanisms involved in the pathogenesis of allergic responses to food antigens in the gut, thereby providing valuable tools for directing novel therapeutic or preventive strategies to the control of allergic enteropathy.
authors.affiliation: School of Medicine of Ribeirão Preto, University of São Paulo, Department of Biochemistry and Immunology, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Cardoso
authors.forename: Pauline R
authors.initials: PR
authors.lastname: Provinciatto
authors.forename: Dannielle F
authors.initials: DF
authors.lastname: Godoi
authors.forename: Beatriz R
authors.initials: BR
authors.lastname: Ferreira
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Teixeira
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Rossi
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
mesh_terms: D000818:Animals; D004751:Enteritis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000276:immunology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics; D005768:Gastrointestinal Hormones / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D020022:Genetic Predisposition to Disease; D007371:Interferon-gamma / Q000235:genetics; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D021183:Peanut Hypersensitivity / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015431:Weight Loss
chemical_list: D050556:Fatty Acid-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D005768:Gastrointestinal Hormones; D053762:Interleukin-12 Subunit p40; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C057275:fatty acid-binding protein 6; D015847:Interleukin-4; D007371:Interferon-gamma