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There have been extensive developments on cellular and molecular mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic infections during the last few years. Better understanding the functions, reciprocal regulation, and counterbalance of subsets of immune and inflammatory cells that interact through interleukins, interferons, TNF-α, and TGF-β offer opportunities for immune interventions and novel treatment modalities in the era of development of biological immune response modifiers particularly targeting these molecules or their receptors. More than 60 cytokines have been designated as interleukins since the initial discoveries of monocyte and lymphocyte interleukins (called IL-1 and IL-2, respectively). Studies of transgenic or gene-deficient mice with altered expression of these cytokines or their receptors and analyses of mutations and polymorphisms in human genes that encode these products have provided essential information about their functions. Here we review recent developments on IL-1 to IL-38, TNF-α, TGF-β, and interferons. We highlight recent advances during the last few years in this area and extensively discuss their cellular sources, targets, receptors, signaling pathways, and roles in immune regulation in patients with allergy and asthma and other inflammatory diseases.

BackgroundDietary changes are suggested to play a role in the increasing prevalence of allergic diseases and asthma. Short‐chain fatty acids (SCFAs) are metabolites present in certain foods and are produced by microbes in the gut following fermentation of fibers. SCFAs have been shown to have anti‐inflammatory properties in animal models. Our objective was to investigate the potential role of SCFAs in the prevention of allergy and asthma.MethodsWe analyzed SCFA levels by high‐performance liquid chromatography (HPLC) in fecal samples from 301 one‐year‐old children from a birth cohort and examined their association with early life exposures, especially diet, and allergy and asthma later in life. Data on exposures and allergic diseases were collected by questionnaires. In addition, we treated mice with SCFAs to examine their effect on allergic airway inflammation.ResultsSignificant associations between the levels of SCFAs and the infant's diet were identified. Children with the highest levels of butyrate and propionate (≥95th percentile) in feces at the age of one year had significantly less atopic sensitization and were less likely to have asthma between 3 and 6 years. Children with the highest levels of butyrate were also less likely to have a reported diagnosis of food allergy or allergic rhinitis. Oral administration of SCFAs to mice significantly reduced the severity of allergic airway inflammation.ConclusionOur results suggest that strategies to increase SCFA levels could be a new dietary preventive option for allergic diseases in children.

Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.

Allergic diseases are considered the epidemics of the twentieth century estimated to affect more than 30% of the population in industrialized countries with a still increasing incidence. During the past two decades, the application of molecular biology allowed cloning, production and characterization of hundreds of recombinant allergens. In turn, knowledge about molecular, chemical and biologically relevant allergens contributed to increase our understanding of the mechanisms underlying IgE-mediated type I hypersensitivity reactions. It has been largely demonstrated that fungi are potent sources of allergenic molecules covering a vast variety of molecular structures including enzymes, toxins, cell wall components and phylogenetically highly conserved cross-reactive proteins. Despite the large knowledge accumulated and the compelling evidence for an involvement of fungal allergens in the pathophysiology of allergic diseases, fungi as a prominent source of allergens are still largely neglected in basic research as well as in clinical practice. This review aims to highlight the impact of fungal allergens with focus on asthma and atopic dermatitis.Allergy is a disease with many faces that can affect different organs like upper and lower respiratory tract, eyes, intestinal tract and the skin. Depending on the affected organ, allergic symptoms manifest as allergic rhinitis (1), allergic asthma (2), IgE-associated atopic dermatitis (3), food allergy (4) or insect venom allergy (5), to mention only the most important ones. The common hallmark of allergic diseases is a switch to the production of allergen-specific IgE raised against normally innocuous environmental allergens (6) that, in special cases, might also cross-react with self-antigens (7,8). At this asymptomatic stage, the individual is sensitized to a given allergenic source due to the presence of allergen-specific IgE in serum, a condition also called 'atopy'. Detection of allergen-specific IgE is considered as a specific biomarker for the atopic state in clinical practice, which allows in most cases a linkage of a symptom to a particular allergen exposure (9). Measurement of allergen-specific IgE antibodies in serum is normally performed with fully automated devices (10) and used to confirm sensitization to a particular allergen in support of a history-based clinical diagnosis of allergy or a symptom-based suspicion. In sensitized (atopic) individuals, however, re-exposure to the offending allergen induces crosslinking of the high-affinity receptor FceRI-bound allergenspecific IgE on effector cells and, thus, immediate release of anaphylactogenic mediators (11). Although the mechanisms leading to allergic reactions (12, 13) and the sources of exposure are quite well known, our knowledge about the repertoire of molecular structures involved in the pathogenesis of allergic reactions is still rudimentary (14) even if it is well recognized that only a minor fraction of the myriad of proteins to which humans are exposed provokes allergic reactions. Bioinfo...