CXC chemokine receptor 3 (CXCR3), predominately expressed on memory/activated T lymphocytes, is a receptor for both IFN-γ-inducible protein-10 (γ IP-10) and monokine induced by IFN-γ (Mig). We report a novel finding that CXCR3 is also expressed on eosinophils. γ IP-10 and Mig induce eosinophil chemotaxis via CXCR3, as documented by the fact that anti-CXCR3 mAb blocks γ IP-10- and Mig-induced eosinophil chemotaxis. γ IP-10- and Mig-induced eosinophil chemotaxis are up- and down-regulated by IL-2 and IL-10, respectively. Correspondingly, CXCR3 protein and mRNA expressions in eosinophils are up- and down-regulated by IL-2 and IL-10, respectively, as detected using flow cytometry, immunocytochemical assay, and a real-time quantitative RT-PCR technique. γ IP-10 and Mig act eosinophils to induce chemotaxis via the cAMP-dependent protein kinase A signaling pathways. The fact that γ IP-10 and Mig induce an increase in intracellular calcium in eosinophils confirms that CXCR3 exists on eosinophils. Besides induction to chemotaxis, γ IP-10 and Mig also activate eosinophils to eosinophil cationic protein release. These results indicate that CXCR3-γ IP-10 and -Mig receptor-ligand pairs as well as the effects of IL-2 and IL-10 on them may be especially important in the cytokine/chemokine environment for the pathophysiologic events of allergic inflammation, including initiation, progression, and termination in the processes.

High-dose, subcutaneous IT is efficacious and safe in patients with severe birch pollen rhinoconjunctivitis and asthma.

Allergic respiratory disease represents a significant and expanding health problem worldwide. Allergic symptoms, such as asthma and hay fever, cause sleep impairment and reduce school and work performance. The cost to society is substantial. Allergen avoidance and pharmacotherapy cannot control the disease. Only allergy immunotherapy has disease-modifying potential and should be included in optimal treatment strategies. Allergy immunotherapy was first administered as subcutaneous injections and has been practiced for the past 100 years or so. Recently, tablet-based sublingual allergy immunotherapy (SLIT) was introduced with comprehensive clinical documentation. SLIT tablets represent a more patient-friendly concept because they can be used for self-treatment at home.

No abstract

Human type 1 immediate allergic response symptoms are caused by mediator release from basophils and mast cells. This event is triggered by allergens aggregating preformed IgE Abs bound to the high-affinity receptor (FcεRI) on these cells. Thus, the allergen/IgE interaction is crucial for the cascade leading to the allergic and anaphylactic response. Two genetically engineered forms of the white birch pollen major allergen Bet v 1 with point mutations directed at molecular surfaces have been characterized. Four and nine point mutations led to a significant reduction of the binding to human serum IgE, suggesting a mutation-induced distortion of IgE-binding B cell epitopes. In addition, the mutated allergens showed a decrease in anaphylactic potential, because histamine release from human basophils was significantly reduced. Retained α-carbon backbone folding pattern of the mutated allergens was indicated by x-ray diffraction analysis and circular dichroism spectroscopy. The rBet v 1 mutants were able to induce proliferation of T cell lines derived from birch pollen allergic patients. The stimulation indices were similar to the indices of nonmutated rBet v 1 and natural Bet v 1 purified from birch pollen. The ability of anti-rBet v 1 mutant specific mouse IgG serum to block binding of human serum IgE to rBet v 1 demonstrates that the engineered rBet v 1 mutants are able to induce Abs reactive with nonmodified Bet v 1. rBet v 1 mutants may constitute vaccine candidates with improved efficacy/safety profiles for safer allergy vaccination.

In the present study, we have established a mouse model displaying the hallmarks of allergic rhinitis using a clinically relevant allergen. Using this model, we have demonstrated that SLIT treatment is able to reduce allergic symptoms in a time- and dose-dependent manner.

The mast cell, which is a histamine-containing cell, has been found to have far more functions in skin inflammation than hitherto understood. To investigate the appearance of mast cells in prurigo nodularis, histamine immunohistochemistry in combination with nerve growth factor receptor (NGFr) double-staining as well as electron microscopic studies were performed. The results revealed that the histamine-containing cell number was increased in the lesional dermis. The mast cell size was also increased and the shape had become more dendritic. They tended to contact the epidermis and even infiltrated into it. In the histamine and NGFr double-staining, both an increased histamine-containing mast cell number and an increased number of NGFr-immunoreactive nerve fiber profiles were revealed in the upper dermis of the prurigo nodularis lesional skin. Mast cells were seen in close vicinity to NGFr-positive nerves and sometimes even seemingly to contact single nerve fibers. At the ultrastructural level, it is obvious that the mast cell bodies become larger, having more abundant cytoplasm and organelles (e.g. mitochondria), but comparatively fewer characteristic granules. Mast cells were often observed to sprout long dendrites, with or without granules. The cells were also frequently seen to contact other cell types, and a mast cell infiltration into the epidermis was also found. The statistical results of mast cell numbers showed a significant increase in prurigo nodularis lesional skin compared to the normal controls. The present results further indicate that mast cells, together with cutaneous nerve fibers, are actively involved in the pathogenesis of the disease.

The results indicate that certain neurons increasingly express CGRP, which may dynamically result in a neurogenic inflammation in the lesional skin, through vasodilatation, and recruitment and regulation of inflammatory cells, e.g. eosinophils and mast cells.