Inhibition of angiogenesis by IL-32: possible role in asthma.

Background: IL-32 is a proinflammatory cytokine involved in various chronic inflammatory diseases. Chronic airway inflammation in asthmatic patients results in structural airway changes, including angiogenesis. Vascular endothelial growth factor (VEGF) is a key inducer of angiogenesis in the airways of asthmatic patients.

Cord blood derived CD4+ CD25(high) T cells become functional regulatory T cells upon antigen encounter.

Background: Upon antigen exposure, cord blood derived T cells respond to ubiquitous environmental antigens by high proliferation. To date it remains unclear whether these "excessive" responses relate to different regulatory properties of the putative T regulatory cell (Treg) compartment or even expansion of the Treg compartment itself.

Methods: Cord blood (>37 week of gestation) and peripheral blood (healthy controls) were obtained and different Treg cell subsets were isolated.

Histamine regulation of innate and adaptive immunity.

Histamine influences many cell types involved in the regulation of innate and adaptive immune responses including antigen-presenting cells (APCs), Natural Killer (NK) cells, epithelial cells, T lymphocytes and B lymphocytes. These cells express histamine receptors (HRs) and also secrete histamine, which can selectively recruit the major effector cells into tissue sites and affect their maturation, activation, polarization and effector functions leading to tolerogenic or pro-inflammatory responses. Histamine and its four receptors represent a complex system of immunoregulation with distinct effects of receptor subtypes and their differential expression, which changes according to the stage of cell differentiation as well as micro-environmental influences.

Bifidobacterium infantis 35624 administration induces Foxp3 T regulatory cells in human peripheral blood: potential role for myeloid and plasmacytoid dendritic cells.

Background: Intestinal homoeostasis is dependent on immunological tolerance to the microbiota.

Objective: To (1) determine if a probiotic could induce Foxp3 T cells in humans; (2) to elucidate the molecular mechanisms, which are involved in the induction of Foxp3 T cells by human dendritic cells.

Design: Cytokine secretion and Foxp3 expression were assessed in human volunteers following Bifidobacterium infantis feeding.

Induction and maintenance of allergen-specific FOXP3+ Treg cells in human tonsils as potential first-line organs of oral tolerance.

Background: Tonsils are strategically located in the gateway of both alimentary and respiratory tracts representing the first contact point of food and aeroallergens with the immune system. Tonsillectomy removes only the palatine tonsils and sometimes adenoids. Lingual tonsil is anatomically big and remains lifelong intact.

Specific immunotherapy and turning off the T cell: how does it work?

Objective: To examine T-regulatory (Treg) cell functions in allergic immune responses and their roles during allergen specific immunotherapy based on recent developments and current understanding of immune regulation.

Data Sources: PubMed search of English-language articles regarding Treg cells and allergen specific immunotherapy.

Study Selection: Articles on the subject matter were selected and reviewed.

T-cell and antibody responses to phospholipase A2 from different species show distinct cross-reactivity patterns.

Background: Secreted phospholipases A2 (sPLA2) represent antigens to which humans may be rarely or frequently exposed. Thus, the investigation of humoral and cellular immune responses to sPLA2s from different species can provide a suitable model in the study of antibody and T-cell cross-reactivity.

Methods: Specific IgE, IgG1, IgG4, and IgA antibodies were analyzed by ELISA against sPLA2s from pancreas of Bos taurus (BT), Apis mellifera (AM) bee venom, Daboia russellii (DR) and Naja mossambica (NM) snake venoms, and human group III (hGIII) sPLA2 using sera of nonallergic beekeepers, AM-allergic patients, and healthy controls.

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.

IL-33 links tissue cells, dendritic cells and Th2 cell development in a mouse model of asthma.

IL-33 is becoming a central molecule in allergic asthma that addresses various cascades of innate and adaptive immune responses that lead to inflammation in the lung. Its effects are exerted via its heterodimeric receptor that consists of ST2 and the ubiquitously expressed IL-1 receptor accessory protein (ILRAcP). IL-33 integrates both innate and adaptive immunity in a unique fashion via basophils, mast cells, eosinophils, innate lymphoid cells, NK and NKT cells, nuocytes, Th2 lymphocytes and a CD34(pos) precursor cell population.

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.

Immunological mechanisms of allergen-specific immunotherapy.

The studies on the mechanisms of specific immunotherapy (SIT) point out its targets that decide on the efficacy of SIT and hence might be used for its further improvement. Several mechanisms have been proposed to explain the beneficial effects of immunotherapy. The knowledge of the mechanisms underlying allergic diseases and curative treatment possibilities has experienced exciting advances over the last three decades.

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.

Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome.

It is increasingly clear that asthma is a complex disease made up of number of disease variants with different underlying pathophysiologies. Limited knowledge of the mechanisms of these disease subgroups is possibly the greatest obstacle in understanding the causes of asthma and improving treatment and can explain the failure to identify consistent genetic and environmental correlations to asthma. Here we describe a hypothesis whereby the asthma syndrome is divided into distinct disease entities with specific mechanisms, which we have called "asthma endotypes.

T-cell subset regulation in atopy.

Presentation of processed allergen by antigen-presenting cells to T-helper (Th) lymphocytes, which is influenced costimulatory signals, cytokines, chemokines, and regulatory T cells (Tregs), determines the development of different types of T-cell immunity. The discovery of Tregs revolutionized the primary concepts of immune regulation interpreted within the framework of a binary Th1/Th2 paradigm. Tregs play a central role in the maintenance of peripheral homeostasis, the establishment of controlled immune responses, and the inhibition of allergen-specific effector cells.

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.

TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis.

Background: Activation of skin keratinocytes followed by their apoptotic death leads to eczema and spongiosis formations in patients with atopic dermatitis (AD). TNF-like weak inducer of apoptosis (TWEAK) binds to its receptor, fibroblast growth factor-inducible 14 (Fn14), and controls many cellular activities, including proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation.

Objective: The aim of the study was to investigate the role of TWEAK and Fn14 in the formation of eczema in patients with AD.