The role of Treg cell subsets in allergic disease

Allergic diseases are caused by a hypersensitivity reaction to an external substance that is normally not harmful to the body. An imbalance between type 2 immune response and regulatory T cells (Tregs) has been found to be effective in immunopathology of allergic diseases. Tregs can inhibit type 2 immune cells such as T helper 2 (Th2), type 2 innate lymphoid cells and IgE-producing B cells; meanwhile, they induce tolerogenic dendritic cells, regulatory B cells and IgG4-producing B cells. Tregs play a critical role in maintaining immune tolerance to allergens that regulate the type 2 immune response in patients with allergic diseases. Allergen-specific immunotherapy (AIT) is the only causal treatment modality to reduce allergic symptoms by altering the immune response to allergens. A key feature of AIT is to induce and maintain immune tolerance to allergens that enhances functionality, while inducing and maintaining Tregs in allergic patients. In this review, we discuss the six subsets of Tregs, natural (nTregs), inducible Treg (iTregs), inducible costimulatory (ICOS+ Tregs), Tr1, CD8+ Tregs and IL-17-producing Tregs, and their role in allergic disease and allergen immune tolerance. We also discuss specific markers of dysregulated Tregs in allergy such as, immunoglobulin-like transcript (ILT) 3, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) and ST2. These novel molecules on Tregs provide an opportunity for novel treatment strategies aimed at changing the function of Tregs in allergic diseases

Environmental factors in epithelial barrier dysfunction

The main interfaces controlling and attempting to homeostatically balance communications between the host and the environment are the epithelial barriers of the skin, gastrointestinal system, and airways. The epithelial barrier constitutes the first line of physical, chemical, and immunologic defenses and provides a protective wall against environmental factors. Following the industrial revolution in the 19th century, urbanization and socioeconomic development have led to an increase in energy consumption, and waste discharge, leading to increased exposure to air pollution and chemical hazards. Particularly after the 1960s, biological and chemical insults from the surrounding environment—the exposome—have been disrupting the physical integrity of the barrier by degrading the intercellular barrier proteins at tight and adherens junctions, triggering epithelial alarmin cytokine responses such as IL-25, IL-33, and thymic stromal lymphopoietin, and increasing the epithelial barrier permeability. A typical type 2 immune response develops in affected organs in asthma, rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, food allergy, and atopic dermatitis. The aim of this article was to discuss the effects of environmental factors such as protease enzymes of allergens, detergents, tobacco, ozone, particulate matter, diesel exhaust, nanoparticles, and microplastic on the integrity of the epithelial barriers in the context of epithelial barrier hypothesis

Immunologic mechanisms in asthma

Asthma is a chronic airway disease, which affects more than 300 million people. The pathogenesis of asthma exhibits marked heterogeneity with many phenotypes defining visible characteristics and endotypes defining molecular mechanisms. With the evolution of novel biological therapies, patients, who do not-respond to conventional asthma therapy require novel biologic medications, such as anti-IgE, anti-IL-5 and anti-IL4/IL13 to control asthma symptoms. It is increasingly important for physicians to understand immunopathology of asthma and to characterize asthma phenotypes. Asthma is associated with immune system activation, airway hyperresponsiveness (AHR), epithelial cell activation, mucus overproduction and airway remodeling. Both innate and adaptive immunity play roles in immunologic mechanisms of asthma. Type 2 asthma with eosinophilia is a common phenotype in asthma. It occurs with and without visible allergy. The type 2 endotype comprises; T helper type 2 (Th2) cells, type 2 innate lymphoid cells (ILC2), IgE-secreting B cells and eosinophils. Eosinophilic nonallergic asthma is ILC2 predominated, which produces IL-5 to recruit eosinophil into the mucosal airway. The second major subgroup of asthma is non-type 2 asthma, which contains heterogeneous group of endoypes and phenotypes, such as exercise-induced asthma, obesity induced asthma, etc. Neutrophilic asthma is not induced by allergens but can be induced by infections, cigarette smoke and pollution. IL-17 which is produced by Th17 cells and type 3 ILCs, can stimulate neutrophilic airway inflammation. Macrophages, dendritic cells and NKT cells are all capable of producing cytokines that are known to contribute in allergic and nonallergic asthma. Bronchial epithelial cell activation and release of cytokines, such as IL-33, IL-25 and TSLP play a major role in asthma. Especially, allergens or environmental exposure to toxic agents, such as pollutants, diesel exhaust, detergents may affect the epithelial barrier leading to asthma development. In this review, we focus on the immunologic mechanism of heterogenous asthma phenotypes