Involvement and therapeutic implications of airway epithelial barrier dysfunction in type 2 inflammation of asthma / 中华医学杂志(英文版)

Type 2 inflammation is a complex immune response and primary mechanism for several common allergic diseases including allergic rhinitis, allergic asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyps. It is the predominant type of immune response against helminths to prevent their tissue infiltration and induce their expulsion. Recent studies suggest that epithelial barrier dysfunction contributes to the development of type 2 inflammation in asthma, which may partly explain the increasing prevalence of asthma in China and around the globe. The epithelial barrier hypothesis has recently been proposed and has received great interest from the scientific community. The development of leaky epithelial barriers leads to microbial dysbiosis and the translocation of bacteria to inter- and sub-epithelial areas and the development of epithelial tissue inflammation. Accordingly, preventing the impairment and promoting the restoration of a deteriorated airway epithelial barrier represents a promising strategy for the treatment of asthma. This review introduces the interaction between type 2 inflammation and the airway epithelial barrier in asthma, the structure and molecular composition of the airway epithelial barrier, and the assessment of epithelial barrier integrity. The role of airway epithelial barrier disruption in the pathogenesis of asthma will be discussed. In addition, the possible mechanisms underlying the airway epithelial barrier dysfunction induced by allergens and environmental pollutants, and current treatments to restore the airway epithelial barrier are reviewed.

Role of Regulatory Cells in Oral Tolerance

The immune system is continuously exposed to great amounts of different antigens from both food and intestinal microbes. Immune tolerance to these antigens is very important for intestinal and systemic immune homeostasis. Oral tolerance is a specific type of peripheral tolerance induced by exposure to antigen via the oral route. Investigations on the role of intestinal immune system in preventing hypersensitivity reactions to innocuous dietary and microbial antigens have been intensively performed during the last 2 decades. In this review article, we discuss how food allergens are recognized by the intestinal immune system and draw attention to the role of regulatory T (Treg) and B (Breg) cells in the establishment of oral tolerance and tolerogenic features of intestinal dendritic cells. We also emphasize the potential role of tonsils in oral tolerance induction because of their anatomical location, cellular composition, and possible usage to develop novel ways of specific immunotherapy for the treatment of allergic diseases.

Mechanisms of immune tolerance to allergens in children / 소아과

Because the prevalence of allergic diseases has significantly increased in recent years, understanding the causes and mechanisms of these disorders is of high importance, and intense investigations are ongoing. Current knowledge pinpoints immune tolerance mechanisms as indispensable for healthy immune response to allergens in daily life. It is evident that development and maintenance of allergens-pecific T cell tolerance is of vital importance for a healthy immune response to allergens. Such tolerance can be gained spontaneously by dose-dependent exposures to allergens in nature or by allergen-specific immunotherapy. Allergen-specific immunotherapy induces regulatory T cells with the capacity to secrete interleukin-10 and transforming growth factor-beta, limits activation of effector cells of allergic inflammation (such as mast cells and basophils), and switches antibody isotype from IgE to the noninflammatory type IgG4. Although allergen-specific immunotherapy is the only method of tolerance induction in allergic individuals, several factors, such as long duration of treatment, compliance problems, and life-threatening side effects, have limited widespread applicability of this immunomodulatory treatment. To overcome these limitations, current research focuses on the introduction of allergens in more efficient and safer ways. Defining the endotypes and phenotypes of allergic diseases might provide the ability to select ideal patients, and novel biomarkers might ensure new custom-tailored therapy modalities.

Update in the Mechanisms of Allergen-Specific Immunotheraphy

Allergic diseases represent a complex innate and adoptive immune response to natural environmental allergens with Th2-type T cells and allergen-specific IgE predominance. Allergen-specific immunotherapy is the most effective therapeutic approach for disregulated immune response towards allergens by enhancing immune tolerance mechanisms. The main aim of immunotherapy is the generation of allergen nonresponsive or tolerant T cells in sensitized patients and downregulation of predominant T cell- and IgE-mediated immune responses. During allergen-specific immunotherapy, T regulatory cells are generated, which secrete IL-10 and induce allergen-specific B cells for the production of IgG4 antibodies. These mechanisms induce tolerance to antigens that reduces allergic symptoms. Although current knowledge highlights the role of T regulatory cell-mediated immunetolerance, definite mechanisms that lead to a successful clinical outcomes of allergen-specific immunotherapy still remains an open area of research.