Severe Allergy as a Chronic Inflammatory Condition From a Systems Biology Perspective.

Persistent and unresolved inflammation is a common underlying factor observed in several and seemingly unrelated human diseases, including cardiovascular and neurodegenerative diseases. Particularly, in atopic conditions, acute inflammatory responses such as those triggered by insect venom, food or drug allergies possess also a life-threatening potential. However, respiratory allergies predominantly exhibit late immune responses associated with chronic inflammation, that can eventually progress into a severe phenotype displaying similar features as those observed in other chronic inflammatory diseases, as is the case of uncontrolled severe asthma. This review aims to explore the different facets and systems involved in chronic allergic inflammation, including processes such as tissue remodelling and immune cell dysregulation, as well as genetic, metabolic and microbiota alterations, which are common to other inflammatory conditions. Our goal here was to deepen on the understanding of an entangled disease as is chronic allergic inflammation and expose potential avenues for the development of better diagnostic and intervention strategies.

Epithelial Barrier: Protector and Trigger of Allergic Disorders.

The epithelial barrier has classically been considered as the only first line of defense against irritants, pathogens, and allergens. However, it is now known to play an essential role in the immune response to exogenous agents. In fact, recent reports postulate the epithelial barrier hypothesis as a possible explanation for the increasing incidence and severity of allergic diseases. The epithelial barrier preserves the isolation of internal tissues from potential external threats. Moreover, a coordinated interaction between epithelial and immune cells ensures the unique immune response taking place in mucosal tissues, which is reported to be dysregulated in allergic diseases. We and others have demonstrated that in severe allergic phenotypes, the epithelial barrier undergoes several histological modifications, with increased infiltration of immune cells, leading to dysfunction. This is common in atopic dermatitis, asthma, and food allergy. However, the precise role of the epithelial barrier in mucosal biology during progression of allergic diseases is not well understood. In this review, we aim to compile recent knowledge regarding the histological structure and immunological function of the epithelial barrier and to shed light on the role of this compartment in the onset and progression of allergic diseases.

Epithelial Barrier: Protector and Trigger of Allergic Disorders

The epithelial barrier has classically been considered as the only first line of defense against irritants, pathogens, and allergens. However,it is now known to play an essential role in the immune response to exogenous agents. In fact, recent reports postulate the epithelialbarrier hypothesis as a possible explanation for the increasing incidence and severity of allergic diseases.The epithelial barrier preserves the isolation of internal tissues from potential external threats. Moreover, a coordinated interaction betweenepithelial and immune cells ensures the unique immune response taking place in mucosal tissues, which is reported to be dysregulatedin allergic diseases.We and others have demonstrated that in severe allergic phenotypes, the epithelial barrier undergoes several histological modifications,with increased infiltration of immune cells, leading to dysfunction. This is common in atopic dermatitis, asthma, and food allergy. However,the precise role of the epithelial barrier in mucosal biology during progression of allergic diseases is not well understood.In this review, we aim to compile recent knowledge regarding the histological structure and immunological function of the epithelialbarrier and to shed light on the role of this compartment in the onset and progression of allergic diseases (AU)

La barrera epitelial se ha considerado clásicamente sólo como la primera línea de defensa contra los irritantes, patógenos y alérgenos,pero ahora sabemos que el epitelio también desempeña un papel esencial en la respuesta inmunológica frente los agentes exógenos.De hecho, informes recientes postulan la hipótesis de la barrera epitelial como una posible explicación de la creciente incidencia y lagravedad de las enfermedades alérgicas.La barrera epitelial preserva el aislamiento de los tejidos internos de las posibles amenazas exteriores. Se sabe que las células epiteliales,además de un papel meramente protector, también tienen una función esencial en el desarrollo de la respuesta inmune en las mucosas,favoreciendo un ambiente tolerogénico. Sin embargo, en enfermedades alérgicas, estas características se ven afectadas como demuestrauna repuesta exagerada ante antígenos inocuos. De hecho, en los fenotipos alérgicos graves, la barrera epitelial experimenta variasmodificaciones histológicas que se asocian con pérdida de integridad y aumento de los infiltrados celulares, lo que conduce a una disfunciónde la misma. Este proceso es común en la dermatitis atópica, el asma y/o la alergia alimentaria. Aunque todavía no se conoce bien lafunción exacta de la barrera epitelial en la biología de la mucosa durante las enfermedades alérgicas.En esta revisión, pretendemos recopilar los conocimientos recientes sobre la estructura histológica y la función inmunológica de la barreraepitelial, y arrojar luz sobre el papel de este compartimento en la aparición y la progresión de las enfermedades alérgicas (AU)