Regulation of the immune response and inflammation by histamine and histamine receptors.

Histamine is a biogenic amine with extensive effects on many cell types, including important immunologic cells, such as antigen-presenting cells, natural killer cells, epithelial cells, and T and B lymphocytes. Histamine and its 4 receptors represent a complex system of immunoregulation with distinct effects dependent on receptor subtypes and their differential expression. These are influenced by the stage of cell differentiation, as well as microenvironmental influences, leading to the selective recruitment of effector cells into tissue sites accompanied by effects on cellular maturation, activation, polarization, and effector functions, which lead to tolerogenic or proinflammatory responses.

Mechanisms of immunotherapy to wasp and bee venom.

Hymenoptera venoms are important allergens that can elicit both local and systemic allergic reactions, including life-threatening anaphylaxis. Venom immunotherapy (VIT) remains the most effective treatment, reducing the risk of systemic reactions in individuals with Hymenoptera venom allergy. VIT can restore normal immunity against venom allergens and provide patients with a lifetime of tolerance to venoms.

Claudin-1 expression in airway smooth muscle exacerbates airway remodeling in asthmatic subjects.

Background: Increased airway smooth muscle (ASM) mass is an essential component of airway remodeling and asthma development, and there is no medication specifically against it. Tight junction (TJ) proteins, which are expressed in endothelial and epithelial cells and affect tissue integrity, might exist in other types of cells and display additional functions in the asthmatic lung.

Objective: The aim of this study was to investigate the existence, regulation, and function of TJ proteins in ASM in asthmatic patients.

Mechanisms of subcutaneous allergen immunotherapy.

Allergen-specific immunotherapy (SIT) is the only curative approach in the treatment of allergic diseases defined up-to-date. Peripheral T-cell tolerance to allergens, the goal of successful allergen-SIT, is the primary mechanism in healthy immune responses to allergens. By repeated administration of increased doses of the causative allergen, allergen-SIT induces a state of immune tolerance to allergens through the constitution of T regulatory (Treg) cells, including allergen-specific interleukin (IL)-10-secreting Treg type 1 cells and CD4(+)CD25(+)Treg cells; induction of suppressive cytokines, such as IL-10 and transforming growth factor β; suppression of allergen-specific IgE and induction of IgG4 and IgA; and suppression of mast cells, basophils, eosinophils, and inflammatory dendritic cells.

NK cell subsets and their role in allergy.

Introduction: NK cells represent a distinct lymphocyte population with extensive cytolytic activity and a variety of other functions, including regulation of hemopoiesis, suppressor functions and immunoglobulin production. Recently, reports suggest that NK cells also display potent regulatory functions via secretion of cytokines or cell-contact-dependent mechanisms. Thus NK cells may regulate innate and adaptive immune responses and play a role in immune homeostasis.

Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases.

Advancing our understanding of mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic infections could lead to effective and targeted therapies. Subsets of immune and inflammatory cells interact via ILs and IFNs; reciprocal regulation and counter balance among T(h) and regulatory T cells, as well as subsets of B cells, offer opportunities for immune interventions. Here, we review current knowledge about ILs 1 to 37 and IFN-γ.

Histamine receptor H1 signaling on dendritic cells plays a key role in the IFN-γ/IL-17 balance in T cell-mediated skin inflammation.

Background: The diverse effects of histamine on immune regulation are a result of the differential expression and regulation of 4 histamine receptors. Many of the immediate allergic and inflammatory actions of histamine are mediated via the type 1 receptor (H1R).

Objectives: We hypothesized that H1R was involved in the fine-tuning of the initiation of T cell-mediated skin pathology-that is, dermatitis.

MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine.

The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and targets for therapy.

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.

Mechanisms of allergen-specific immunotherapy.

Allergen-specific immunotherapy has been used for 100 years as a desensitizing therapy for allergic diseases and represents the potentially curative and specific method of treatment. The mechanisms of action of allergen-specific immunotherapy include the very early desensitization effects, modulation of T-and B-cell responses and related antibody isotypes, and migration of eosinophils, basophils, and mast cells to tissues, as well as release of their mediators. Regulatory T (Treg) cells have been identified as key regulators of immunologic processes in peripheral tolerance to allergens.

The cellular orchestra in skin allergy; are differences to lung and nose relevant?

Purpose Of Review: It has been a long lasting question that although a similar peripheral allergen-specific immune response has been observed, why some patients show only atopic dermatitis, rhinitis and asthma alone or their combinations. The answer resides in the propensity of resident tissue cells and local antigen-presenting cells and T cells for developing an allergic inflammatory immune response. Antigen-presenting cells introduce processed allergens to T helper lymphocytes, where a decision of developing different types of T cell immunity is given under the influence of several cytokines, chemokines, costimulatory signals and regulatory T cells.

The effect of CD14 C159T polymorphism on in vitro IgE synthesis and cytokine production by PBMC from children with asthma.

Background: Even though the genotype at the promoter region of the CD14 molecule is known to affect the atopic phenotypes, the cellular and molecular basis of this association is largely unknown.

Objective: To investigate the effect of lipopolysaccharide (LPS) on IgE production and cytokine profile by peripheral blood mononuclear cells (PBMC) obtained from asthmatic children with the TT and the CC genotypes at position -159 of the CD14 gene.

Methods: Peripheral blood mononuclear cells from asthmatic children with alternative genotypes at CD14 C159T locus were stimulated with 2 and 200 ng/ml LPS in vitro.

T-cell response to allergens.

Anaphylaxis is a life-threatening IgE-dependent type 1 hypersensitivity reaction in which multiple organ systems are involved. The existence of allergen exposure and specific IgE are the major contributors to this systemic reaction. The decision of the immune system to respond to allergens is highly dependent on factors including the type and load of allergen, behavior and type of antigen-presenting cells, innate immune response stimulating substances in the same micromilieu, the tissue of exposure, interactions between T and B lymphocytes, costimulators, and genetic propensity known as atopy.

Novel immunotherapeutic approaches for allergy and asthma.

The immune response is a tightly regulated process, which normally results in protection from infection and tolerance of innocuous environmental antigens. However, in allergic disease, the activated immune response results in a chronic pro-inflammatory state characterized by antibody secretion (IgE) and T cell activation to normally well-tolerated antigens. Currently, the treatment of allergic disease is focused on the suppression of key inflammatory mediators or inflammatory cell populations and include anti-histamines, anti-leukotrienes, β2 adrenergic receptor agonists and corticosteroids.

IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis.

Background: Keratinocyte (KC) apoptosis is an important mechanism of eczema and spongiosis in patients with atopic dermatitis (AD) and is mediated by IFN-gamma, which is secreted by T(H)1 cells. IL-32 is a proinflammatory cytokine that is involved in the inflammatory processes of rheumatoid arthritis, chronic obstructive pulmonary disease, and Crohn disease. Recently, it was shown that upregulation of IL-32 induces apoptosis.

Role of Treg in immune regulation of allergic diseases.

Allergy is a Th2-mediated disease that involves the formation of specific IgE antibodies against innocuous environmental substances. The prevalence of allergic diseases has dramatically increased over the past decades, affecting up to 30% of the population in industrialized countries. The understanding of mechanisms underlying allergic diseases as well as those operating in non-allergic healthy responses and allergen-specific immunotherapy has experienced exciting advances over the past 15 years.

Histamine, histamine receptors and their role in immune pathology.

The important roles of histamine in body physiology and various pathologic events have been well established, whereas new and exciting findings are still being uncovered. Histamine is not only the major mediator of the acute inflammatory and immediate hypersensitivity responses, but has also been demonstrated to affect chronic inflammation and regulate several essential events in the immune response. The diverse effects of histamine on immune regulation are due to the differential expression and regulation of four histamine receptors (HR) and their distinct intracellular signals.

Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3+ inducible regulatory T cells.

Forkhead box P3 (FOXP3)(+)CD4(+)CD25(+) inducible regulatory T (iT reg) cells play an important role in immune tolerance and homeostasis. In this study, we show that the transforming growth factor-beta (TGF-beta) induces the expression of the Runt-related transcription factors RUNX1 and RUNX3 in CD4(+) T cells. This induction seems to be a prerequisite for the binding of RUNX1 and RUNX3 to three putative RUNX binding sites in the FOXP3 promoter.

Immune tolerance in allergy.

Research on the mechanisms of immune regulation in allergy and asthma has shown substantial progress in recent years and has led to a variety of allergen-specific therapeutic and preventive approaches. Studies on the area of allergen-specific immunotherapy (allergen-SIT) have provided substantial knowledge on the mechanisms of allergic disease with novel developments for treatment and prevention. Several studies have demonstrated that increased numbers and the activation of allergen-specific T regulatory cells correlate with successful allergen-SIT.

Therapeutic manipulation of immune tolerance in allergic disease.

Immune tolerance - the adaptation of the immune system to external antigens or allergens - might be therapeutically manipulated to restore normal immunity in conditions such as allergy, asthma and autoimmune diseases. The field of allergen-specific immunotherapy is experiencing exciting and novel developments for the treatment of allergic and autoimmune diseases, and recent insights into the reciprocal regulation and counter-balance between different T-cell subsets is foreseen to facilitate new strategies for immunointervention. This Review highlights current knowledge of immunomodulatory therapies for the manipulation of immune tolerance and highlights recent approaches to improve allergen-specific immunotherapy for the treatment of allergic diseases.

T regulatory cells and their counterparts: masters of immune regulation.

The interaction of environmental and genetic factors with the immune system can lead to the development of allergic diseases. The essential step in this progress is the generation of allergen-specific CD4(+) T-helper (Th) type 2 cells that mediate several effector functions. The influence of Th2 cytokines leads to the production of allergen-specific IgE antibodies by B cells, development and recruitment of eosinophils, mucus production and bronchial hyperreactivity, as well as tissue homing of other Th2 cells and eosinophils.

T cells and eosinophils in bronchial smooth muscle cell death in asthma.

Background: Bronchial smooth muscle cells (SMC) proliferate, express adhesion molecules, secrete cytokines and thus efficiently contribute to the pathogenesis of asthma.

Objective: The aim of the study was to investigate whether, and by which mechanism, T cells and eosinophils can cause death of airway SMC.

Methods: The T cell- and eosinophil-induced cell death was analysed in primary human bronchial SMC cultures as well as in bronchial biopsy specimens from non-asthmatic and asthmatic individuals.

Mechanisms and treatment of allergic disease in the big picture of regulatory T cells.

Various populations of regulatory T (Treg) cells have been shown to play a central role in the maintenance of peripheral homeostasis and the establishment of controlled immune responses. Their identification as key regulators of immunologic processes in peripheral tolerance to allergens has opened an important era in the prevention and treatment of allergic diseases. Both naturally occurring CD4+CD25+ Treg cells and inducible populations of allergen-specific, IL-10-secreting Treg type 1 (T(R)1) cells inhibit allergen-specific effector cells in experimental models.

In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure.

High dose bee venom exposure in beekeepers by natural bee stings represents a model to understand mechanisms of T cell tolerance to allergens in healthy individuals. Continuous exposure of nonallergic beekeepers to high doses of bee venom antigens induces diminished T cell-related cutaneous late-phase swelling to bee stings in parallel with suppressed allergen-specific T cell proliferation and T helper type 1 (Th1) and Th2 cytokine secretion. After multiple bee stings, venom antigen-specific Th1 and Th2 cells show a switch toward interleukin (IL) 10-secreting type 1 T regulatory (Tr1) cells.

IL-10 suppresses CD2-mediated T cell activation via SHP-1.

Interleukin (IL)-10 is an essential suppressive cytokine and plays a key role in peripheral T cell tolerance to allergens, autoantigens, transplantation antigens and tumor antigens. However, the molecular mechanisms of direct T cell suppression by IL-10 are not fully understood. Here, we demonstrate that IL-10 directly inhibits CD2 signaling in T cells.