Associations between Environmental dust composition and Atopic Dermatitis in urban and rural settings.

Background: Environmental exposures are involved in the pathogenesis of the allergic phenotype and in determining which individual triggers a person becomes sensitized to. Atopic dermatitis (AD) may modulate these effects through increased penetration through the skin modifying the immune system and AD may be triggered or intensified by environmental exposures. These exposures and immune-modulating factors may differ in urban and rural environments.

Deletion of IL-4Rα signaling on B cells limits hyperresponsiveness depending on antigen load.

Background: B cells play an important role in allergies through secretion of IgE. IL-4 receptor α (IL-4Rα) is key in allergic asthma and regulates type 2 cytokine production, IgE secretion, and airway hyperresponsiveness. IL-4 activation of B cells is essential for class switching and contributes to the induction of B effector 2 (Be2) cells.

IL-4Rα signaling in CD4+CD25+FoxP3+ T regulatory cells restrains airway inflammation via limiting local tissue IL-33.

Impaired tolerance to innocuous particles during allergic asthma has been linked to increased plasticity of FoxP3+ regulatory T cells (Tregs) reprogramming into pathogenic effector cells, thus exacerbating airway disease. However, failure of tolerance mechanisms is driven by Th2 inflammatory signals. Therefore, the in vivo role of canonical IL-4 receptor α (IL-4Rα) signaling, an essential driver of Th2-type airway responses to allergens, on the regulatory function of FoxP3+ Tregs in allergic asthma was explored.

Therapeutic and prophylactic deletion of IL-4Ra-signaling ameliorates established ovalbumin induced allergic asthma.

Background: Allergic asthma is a chronic inflammatory airway disease driven predominantly by a T 2 immune response to environmental allergens. IL-4Rα-signaling is essential for driving T 2-type immunity to allergens. Anti-T 2 therapies have the potential to effectively reduce airway obstruction and inflammation in allergic asthma.

Author Correction: House dust mite induced allergic airway disease is attenuated in CD11cIL-4Rα° mice.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

House dust mite induced allergic airway disease is attenuated in CD11cIL-4Rα° mice.

The precise mechanisms leading to development of T helper type (Th)2-driven allergic responses are unknown. We aimed to determine how IL-4 receptor alpha (IL-4Rα) signaling on CD11c cells influences allergen-induced Th2 responses in mice. CD11cIL-4Rα° mice, deficient in IL-4Rα on dendritic cells and alveolar macrophages, were compared to IL-4Rα° littermate controls in models of allergic airway disease induced by OVA/alum, OVA alone or house dust mite.

β-Glucan exacerbates allergic airway responses to house dust mite allergen.

β-(1,3)-Glucan is present in mould cell walls and frequently detected in house dust mite (HDM) faeces. β-Glucan exposure is thought to be associated with pulmonary allergic inflammation in mouse and man, although the published data are inconsistent. Here, we show that highly purified β-glucan exacerbates HDM-induced eosinophilic, T helper 2 type airway responses by acting as an adjuvant, promoting activation, proliferation and polarisation of HDM-specific T cells (1-Derβ T cells).

Role of IL-4 receptor α-positive CD4(+) T cells in chronic airway hyperresponsiveness.

Background: TH2 cells and their cytokines are associated with allergic asthma in human subjects and with mouse models of allergic airway disease. IL-4 signaling through the IL-4 receptor α (IL-4Rα) chain on CD4(+) T cells leads to TH2 cell differentiation in vitro, implying that IL-4Rα-responsive CD4(+) T cells are critical for the induction of allergic asthma. However, mechanisms regulating acute and chronic allergen-specific TH2 responses in vivo remain incompletely understood.

Microbial Ligand Costimulation Drives Neutrophilic Steroid-Refractory Asthma.

Asthma is a heterogeneous disease whose etiology is poorly understood but is likely to involve innate responses to inhaled microbial components that are found in allergens. The influence of these components on pulmonary inflammation has been largely studied in the context of individual agonists, despite knowledge that they can have synergistic effects when used in combination. Here we have explored the effects of LPS and β-glucan, two commonly-encountered microbial agonists, on the pathogenesis of allergic and non-allergic respiratory responses to house dust mite allergen.

The M3 muscarinic receptor is required for optimal adaptive immunity to helminth and bacterial infection.

Innate immunity is regulated by cholinergic signalling through nicotinic acetylcholine receptors. We show here that signalling through the M3 muscarinic acetylcholine receptor (M3R) plays an important role in adaptive immunity to both Nippostrongylus brasiliensis and Salmonella enterica serovar Typhimurium, as M3R-/- mice were impaired in their ability to resolve infection with either pathogen. CD4 T cell activation and cytokine production were reduced in M3R-/- mice.

IL-4Rα-associated antigen processing by B cells promotes immunity in Nippostrongylus brasiliensis infection.

In this study, B cell function in protective T(H)2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4.

Interruption of CD28-mediated costimulation during allergen challenge protects mice from allergic airway disease.

Background: Allergic asthma is a T(H)2-promoted hyperreactivity with an immediate, IgE, and mast cell-dependent response followed by eosinophil-dominated inflammation and airway obstruction.

Objective: Because costimulation by CD28 is essential for T(H)2 but not T(H)1 responses, we investigated the effect of selective interference with this pathway in mice using the models of ovalbumin and house dust mite-induced airway inflammation.

Methods: To study the role of CD28 in the effector phase of allergic airway inflammation, we developed an inducibly CD28-deleting mouse strain or alternatively used a CD28 ligand-binding site-specific mouse anti-mouse mAb blocking CD28 engagement.

Allergic airway disease is unaffected by the absence of IL-4Rα-dependent alternatively activated macrophages.

Background: Markers of alternatively activated macrophages (AAMs) are upregulated in the lungs of asthmatic patients and in mice with allergic airway disease. AAMs are thought to contribute to the pathogenesis of allergic airway disease by virtue of their decreased NO production and increased production of proline and polyamines, which are important in the synthesis of connective tissues such as collagen.

Objective: We aimed to define the role of AAMs in the pathogenesis of allergic airway disease.

B cells that produce immunoglobulin E mediate colitis in BALB/c mice.

Background & Aims: Induction of colitis in mice by administration of oxazolone is mediated by T-helper (Th) 2 cells and has features of human ulcerative colitis. We investigated whether activation of interleukin (IL)-4Rα on T and B cells determines their effector functions and mediates oxazolone-induced colitis.

Methods: We studied induction of colitis with oxazolone in wild-type mice and those with CD4(+) T cells that did not express IL-4Rα (Lck(cre)IL-4Rα(-/lox)).

Differential responses to natural and recombinant allergens in a murine model of fish allergy.

Aerosolized fish proteins are an important cause of allergic airway reactions in both the domestic and the occupational environment. The aim of this study was to investigate inhalant fish-induced allergy in a mouse model and compare immune responses generated by raw and heat-treated fish extracts as well as natural and recombinant forms of the major fish allergen parvalbumin. Mice were sensitized with raw or cooked pilchard extract and challenged intranasally with cooked pilchard extract, purified natural pilchard parvalbumin or recombinant carp parvalbumin (rCyp c1.

Investigation of in vitro and in vivo anti-asthmatic properties of Siphonochilus aethiopicus.

Aim Of The Study: Asthma is a chronic inflammatory disease of the lungs, characterized by increased sensitivity to bronchoconstriction associated with infiltration of immune cells, mucus hypersecretion and structural remodelling of the airways. In South Africa, the indigenous plant Siphonochilus aethiopicus, is used by traditional health practitioners to treat colds, wheezing of the chest, coughs, influenza, sinus problems and mild asthma. In this study we aimed to investigate the potential anti-inflammatory and anti-allergic properties of S.

Anisakis pegreffii-induced airway hyperresponsiveness is mediated by gamma interferon in the absence of interleukin-4 receptor alpha responsiveness.

Infection with the fish parasite Anisakis following exposure to contaminated fish can lead to allergic reactions in humans. The present study examined the immunological mechanisms underlying the development of allergic airway inflammation in mice after different routes of sensitization to Anisakis. Wild-type and interleukin-4 receptor alpha (IL-4Ralpha)-deficient BALB/c mice were sensitized intraperitoneally with live or heat-killed Anisakis larvae or by intranasal administration of an Anisakis extract and were subsequently challenged intranasally with an Anisakis extract.

Expression of IL-4 receptor alpha on smooth muscle cells is not necessary for development of experimental allergic asthma.

Background: Airflow in the lungs of patients with allergic asthma is impaired by excessive mucus production and airway smooth muscle contractions. Elevated levels of the cytokines IL-4 and IL-13 are associated with this pathology. In vitro studies have suggested that IL-4 receptor alpha (IL-4Ralpha) signaling on smooth muscle cells is critical for airway inflammation and airway hyperresponsiveness.

Interleukin-4-promoted T helper 2 responses enhance Nippostrongylus brasiliensis-induced pulmonary pathology.

The role of CD4(+) T-cell interleukin-4 (IL-4) receptor alpha (IL-4Ralpha) expression in T helper 2 (TH2) immune responses has not been defined. To examine this role, we infected CD4(+) T-cell IL-4Ralpha knockout (KO) mice with the parasitic nematode Nippostrongylus brasiliensis, which induces strong host TH2 responses. Although N.

Occupational allergy to latex among loom tuners in a textile factory.

Background: Occupational allergy to latex is generally reported from occupational groups such as health care workers; however, few reports derive from other occupational settings.

Methods: Two male subjects working as loom tuners in a textile manufacturing plant developed severe allergic reactions during the cutting and weaving of elastic bands, initially not suspected to contain latex constituents. Clinical evaluation and lung function tests were supplemented by skin prick testing, specific IgE evaluation and basophil activation assays with extracted elastic bands.