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Epithelial/immune interactions are characterized by the different properties of the various epithelial tissues, the mediators involved, and the varying immune cells that initiate, sustain, or abrogate allergic diseases on the surface. The intestinal mucosa, respiratory mucosa, and regular skin feature structural differences according to their primary function and surroundings. In the context of these specialized functions, the active role of the epithelium in shaping immune responses is increasingly recognizable. Crosstalk between epithelial and immune cells plays an important role in maintaining homeostatic conditions. While cells of the myeloid cell lineage, mainly macrophages, are the dominating immune cell population in the skin and the respiratory tract, lymphocytes comprise most intraepithelial immune cells in the intestine under healthy conditions. Common to all surface epithelia is the fact that innate immune cells represent the first line of immunosurveillance that either directly defeats invading pathogens or initiates and coordinates more effective successive immune responses involving adaptive immune cells and effector cells. Pharmacological approaches for the treatment of allergic and chronic inflammatory diseases involving epithelial barriers target immunological mediators downstream of the epithelium (such as IL‐4, IL‐5, IL‐13, and IgE). The next generation of therapeutics involves upstream events of the inflammatory cascade, such as epithelial‐derived alarmins and related mediators. [ABSTRACT FROM AUTHOR]

Allergic diseases of the (upper and lower) airways, the skin and the gastrointestinal tract, are on the rise, resulting in impaired quality of life, decreased productivity, and increased healthcare costs. As allergic diseases are mostly tissue‐specific, local sampling methods for respective biomarkers offer the potential for increased sensitivity and specificity. Additionally, local sampling using noninvasive or minimally invasive methods can be cost‐effective and well tolerated, which may even be suitable for primary or home care sampling. Non‐ or minimally invasive local sampling and diagnostics may enable a more thorough endotyping, may help to avoid under‐ or overdiagnosis, and may provide the possibility to approach precision prevention, due to early diagnosis of these local diseases even before they get systemically manifested and detectable. At the same time, dried blood samples may help to facilitate minimal‐invasive primary or home care sampling for classical systemic diagnostic approaches. This EAACI position paper contains a thorough review of the various technologies in allergy diagnosis available on the market, which analytes or biomarkers are employed, and which samples or matrices can be used. Based on this assessment, EAACI position is to drive these developments to efficiently identify allergy and possibly later also viral epidemics and take advantage of comprehensive knowledge to initiate preventions and treatments. [ABSTRACT FROM AUTHOR]

The prevalence of allergic diseases such as allergic rhinitis, asthma, food allergy, and atopic dermatitis has increased dramatically during the last decades, which is associated with altered environmental exposures and lifestyle practices. The purpose of this review was to highlight the potential role for dietary fatty acids, in the prevention and management of these disorders. In addition to their nutritive value, fatty acids have important immunoregulatory effects. Fatty acid‐associated biological mechanisms, human epidemiology, and intervention studies are summarized in this review. The influence of genetics and the microbiome on fatty acid metabolism is also discussed. Despite critical gaps in our current knowledge, it is increasingly apparent that dietary intake of fatty acids may influence the development of inflammatory and tolerogenic immune responses. However, the lack of standardized formats (ie, food versus supplement) and standardized doses, and frequently a lack of prestudy serum fatty acid level assessments in clinical studies significantly limit our ability to compare allergy outcomes across studies and to provide clear recommendations at this time. Future studies must address these limitations and individualized medical approaches should consider the inclusion of specific dietary factors for the prevention and management of asthma, food allergy, and atopic dermatitis. [ABSTRACT FROM AUTHOR]

Recent observations indicate that autoimmune disorders and allergies are more closely connected to each other than traditionally considered. Both diseases are characterized by a break of immunological tolerance and in both Th1- and Th2-driven mechanisms may be involved. Moreover, patients suffering from severe chronic atopic diseases have been shown to develop autoreactive antibodies and vice versa autoreactive IgE antibodies may contribute to the perpetuation of allergic immune responses. However, animal models for the investigation of the underlying mechanisms have not been available so far. Here we demonstrate that allergic sensitization and subsequent airway aerosol challenge of mice to a potential autoantigen leads to an allergic airway inflammation and chronic exposure of sensitized mice to a foreign allergen induces autoreactive antibodies. Thus, autoreactive immune mechanisms may be induced either by molecular mimicry or as a consequence of chronic allergic inflammatory processes and these reactivities may then possibly contribute to the perpetuation of allergic immune responses even in the absence of exogenous allergens and to the development of autoimmune diseases. [ABSTRACT FROM AUTHOR]

Summary: Allergic diseases are inflammatory disorders that develop on the basis of complex gene–environment interactions. The prevalence of allergies is steadily increasing and seems to be associated with modern lifestyle. Therefore, it was hypothesized that high living standards and hygienic conditions are correlated with an increased risk for the development of an allergic disease. This so-called “hygiene hypothesis” states that due to reduced exposure to microbial components, the proposed allergy-preventing potential of these factors is no more present in sufficient qualities and/or quantities, which leads to an imbalance of the immune system with a predisposition to the development of allergic disorders. Meanwhile, several epidemiological studies were conducted supporting this concept and generating novel ideas for the underlying mechanisms that were then followed up by use of well-defined animal models and human studies. The current view of cellular and molecular mechanisms responsible for these phenomena includes changes in the fine balancing of T helper cell 1 (Th1), Th2 and regulatory T cell (Treg) responses which are triggered by altered or missing innate immune cell activation. In fact, proper activation of cells of the innate immune system via their so-called pattern recognition receptors has been demonstrated to play a crucial role in early shaping of the immune system and suppression of the development of Th2-driven allergic immune responses. These processes start already in utero and prenatal as well as early postnatal developmental stages seem to represent a certain “window of opportunity” for allergy-preventing environmental influences. [Copyright &y& Elsevier]

Background: Children who grow up in a farming environment show lower levels of atopic sensitization, hay fever, and asthma than children of the same age not living in such an environment. A number of investigations provided good evidence that this is due to an early-life contact with cowsheds, farm animals, and/or consumption of products like raw milk. Also, it had been indicated that microorganisms might have an important effect on the development of allergies, and thus the question arose of which farm microbial organisms, their products, or both might induce or influence allergy-protective mechanisms. Objective: We sought to gain further insight into the potential allergy-protective properties of microbes isolated from the farming environment. Methods: Of a number of bacterial species identified in cowsheds of farms, 2 were selected, isolated, and characterized, namely Acinetobacter lwoffii F78 and Lactococcus lactis G121. The isolates were investigated with regard to their activation of pattern-recognition receptors, the maturation of human monocyte-derived dendritic cells, the upregulation of inflammatory cytokines, the TH1-polarizing Notch ligand expression, and their influence on the allergic phenotype. Results: It is shown that both bacterial isolates were able to reduce allergic reactions in mice, to activate mammalian cells in vitro, and to induce a TH1-polarizing program in dendritic cells. Conclusion: Our data strongly support the hygiene hypothesis, which states that an environment rich in microbiologic structures, such as a farming environment, might protect against the development of allergies. Clinical implications: This work provides the first data on a potential application of cowshed bacteria in allergy protection. [Copyright &y& Elsevier]

Type I allergy is a classical Th2-driven hypersensitivity disease based on IgE recognition of environmental allergens. Exposure of allergic individuals to exogenous allergens leads to immediate type inflammation caused by degranulation of mast cells via IgE-allergen immune complexes and the release of inflammatory mediators, proteases and pro-inflammatory cytokines. However, allergic inflammation can occur and persist in the absence of exposure to exogenous allergens and might paradoxically resemble a Th1-mediated chronic inflammatory reaction. We summarize evidence supporting the view that autoimmune mechanisms might contribute to these processes. IgE recognition of autoantigens might augment allergic inflammation in the absence of exogenous allergen exposure. Moreover, autoantigens that activate Th1-immune responses could contribute to chronic inflammation in allergy, thus linking allergy to autoimmunity. [Copyright &y& Elsevier]