Immune Basis of Allergic Reactions to Food.

Food allergies are diseases where the normal tolerance response to oral antigens is altered. Recent advances have begun to uncover mechanisms that mediate sensitization to food allergens and maintenance of the disease. Production of alarmins by epithelial cells triggers a cascade that leads to allergen-specific IgE synthesis. IL-9 has also been shown to play a role in mast cell recruitment and amplification of the allergic response. In recent years, increasing evidence suggests that sensitization to food allergens can be developed via nonoral routes, in particular the skin, thus leading to the "dual exposure hypothesis". Environmental factors such as diet or microbiota can shape the immune system to promote tolerance or sensitization to food antigens. While the mechanism of primary tolerance to food antigens is quite clear, that leading to permanent tolerance in food-allergic individuals through immunotherapy is still under study. Understanding the mechanisms by which oral tolerance is suppressed and sensitization develops will help to identify new targets to develop combined therapies for the treatment of food allergies.

Immune basis of allergic reactions to food

Food allergies are diseases where the normal tolerance response to oral antigens is altered. Recent advances have begun to uncover mechanisms that mediate sensitization to food allergens and maintenance of the disease. Production of alarmins by epithelial cells triggers a cascade that leads to allergen-specific IgE synthesis. IL-9 has also been shown to play a role in mast cell recruitment and amplification of the allergic response. In recent years, increasing evidence suggests that sensitization to food allergens can be developed via nonoral routes, in particular the skin, thus leading to the "dual exposure hypothesis". Environmental factors such as diet or microbiota can shape the immune system to promote tolerance or sensitization to food antigens. While the mechanism of primary tolerance to food antigens is quite clear, that leading to permanent tolerance in food-allergic individuals through immunotherapy is still under study. Understanding the mechanisms by which oral tolerance is suppressed and sensitization develops will help to identify new targets to develop combined therapies for the treatment of food allergies

La alergia alimentaria es una enfermedad en la que la respuesta fisiológica normal de tolerancia a los antígenos orales se encuentra alterada. Los nuevos avances en la investigación han comenzado a desvelar los mecanismos que median tanto en la sensibilización a los alérgenos alimentarios como en la persistencia de la enfermedad. La producción de alarminas por parte de las células epiteliales desencadena una cascada que conduce a la síntesis de IgE específica frente a los alérgenos alimentarios. También se ha identificado el papel de la IL-9 en el reclutamiento de mastocitos y la amplificación de la respuesta alérgica. Además en estos últimos años se han completado diversas investigaciones que sugieren que la sensibilización a los alérgenos alimentarios puede desarrollarse por vías no orales, en particular a través de la piel, lo cual ha llevado a la propuesta de la denominada "hipótesis de la doble exposición". Por último, factores ambientales como la dieta o la microbiota pueden moldear el sistema inmunológico para promover la tolerancia o la sensibilización a los antígenos alimentarios. Si bien el mecanismo de tolerancia primaria a los antígenos alimentarios es bastante claro, el que conduce a la tolerancia permanente en individuos que ya tienen alergia a los alimentos a través de la inmunoterapia aún está en estudio. Comprender los mecanismos mediante los cuales se suprime la tolerancia oral y se desarrolla la sensibilización ayudará a identificar nuevos objetivos para desarrollar terapias combinadas para el tratamiento de alergias alimentarias

Hydrolysed ovalbumin offers more effective preventive and therapeutic protection against egg allergy than the intact protein.

BACKGROUND: The application of specific immunotherapy to stimulate oral tolerance towards food allergens is hampered by the high frequency of adverse side-effects and the excessive duration of the treatments. OBJECTIVE: In this work, a hydrolysate of ovalbumin with pepsin (OP), selected for its low IgE reactivity and Th2-stimulating capacity, was assayed for its ability to prevent and treat allergy to egg white (EW). METHODS: As a first step, the safety of OP, in terms of the absence of sensitizing and eliciting potential, was evaluated in BALB/c mice. Then, its suitability for prophylactic and therapeutic applications was compared with that of the intact allergen, paying attention to the molecular and cellular mechanisms involved in the control of the allergic process. To this aim, IgE, IgG1, IgG2a and IgA levels, allergic reactions, expression of genes related to Th1, Th2, Th17 and Treg responses, dendritic and T cell populations were assessed in intestinal tissues and spleens of EW-allergic mice, either untreated or treated with intact ovalbumin (OVA) or OP. RESULTS: The hydrolysate of OVA with pepsin was hypoallergenic, lacked sensitizing potential and offered preventive and therapeutic protection against allergy to EW through the induction of Treg cells and the up-regulation of TGF-ß, IL-10, IL-17, Foxp3 and RORγt in intestinal tissues. This restrained the expression of GATA3 and the differentiation of Th2 cells, leading to low cytokine responses following ex vivo spleen cell stimulation. As compared with intact OVA, OP was more effective against sensitization. In addition, in the therapeutic setting, OP provided quicker desensitization that lasted for at least 3 weeks after discontinuation of the therapy. CONCLUSIONS AND CLINICAL RELEVANCE: This study provides evidence for the superior role of hydrolysed, as compared to intact allergens, in the prevention of allergy development and in the promotion of long-term desensitization, as well as of intermolecular tolerance.

Intragastric administration of Lactobacillus casei BL23 induces regulatory FoxP3+RORγt+ T cells subset in mice.

Many studies have highlighted the immunomodulatory properties of the probiotic strain Lactobacillus casei BL23. Recently, we demonstrated the ability of this strain to modulate the Th2-oriented immune response in a mouse model of cow's milk allergy based on the induction of a Th17-biased immune response. The probiotic function of L. casei has been also linked to gut-microbiota modifications which could been potentially involved in the immune regulation; however, its precise mechanism of action remains poorly understood. In this regard, recent studies suggest that gut microbiota induces a specific subset of CD4+FoxP3+ Treg cells that also express RORγt+, the specific transcription factor of Th17 cells. This new type of regulatory T cells, called type 3 Treg, displays suppressive function during intestinal inflammation, participating in inflammation control. We thus explored the ability of L. casei BL23 to specifically induce type 3 Treg cells, both in vitro and in vivo. Our results showed that intragastric administration of L. casei BL23 to mice induces local and systemic FoxP3+ RORγt+ type 3 Treg cells that could then participate in the beneficial effects of L. casei BL23 in different intestinal-related disorders.