Selective AhR knockout in langerin-expressing cells abates Langerhans cells and polarizes Th2/Tr1 in epicutaneous protein sensitization

The aryl hydrocarbon receptor (AhR) represents an environmental sensor regulating immune responses. In the skin, AhR is expressed in several cell types, including keratinocytes, epidermal Langerhans cells (LC), and dermal dendritic cells (DC). The mechanisms how AhR activates or inhibits cutaneous immune responses remain controversial, owing to differences in the cell-specific functions of AhR and the different activating ligands. Therefore, we sought to investigate the role of AhR in LC and langerin+and negative DC in the skin. To this aim, we generated Langerin-specific and CD11c-specific knockout (−/−) mice lacking AhR, respectively, in LC and Langerin+dermal DC and in all CD11c+cells. These were then tested in an epicutaneous protein (ovalbumin, Ova) sensitization model. Immunofluorescence microscopy and flow cytometry revealed that Langerin-AhR−/−but not CD11c-AhR−/−mice harbored a decreased number of LC with fewer and stunted dendrites in the epidermis as well as a decreased number of LC in skin-draining lymph nodes (LN). Moreover, in the absence of AhR, we detected an enhanced T helper type-2 (Th2) [increased interleukin 5 (IL-5) and interleukin 13 (IL-13)] and T regulatory type-1 (Tr1) (IL-10) response when LN cells were challenged with Ova in vitro, though the number of regulatory T cells (Treg) in the LN remained comparable. Langerin-AhR−/−mice also exhibited increased blood levels of Ova-specific immunoglobulin E (IgE). In conclusion, deletion of AhR in langerin-expressing cells diminishes the number and activation of LC, while enhancing Th2 and Tr1 responses upon epicutaneous protein sensitization.

Soy Skin Prick Test in Patients with Physician-Diagnosed Atopic Disorders

Background Soy protein is an important component of soybeans and is one the 8 most significant food allergens. Yet, the prevalence of soy allergy in the pediatric population is not well defined. Objectives To evaluate the incidence of IgE mediated soy protein sensitization among children with clinical manifestation of atopic disorders by the use of skin prick test (SPT) for soy protein. Methods Two hundred patients with atopic manifestations attending the Pediatric Allergy and Immunology Clinic at the Pediatric Department of Ain shams University, were recruited between January 2017 till January 2018. They were subjected to SPT to soy protein, measurement of total serum IgE and eosinophilic count in the peripheral blood. Results Of the 200 patients, 108 (54%) were males and 92 (46%) were females with a male to female ratio of 1.17:1. Their ages ranged between 2 years and 15 years (mean±SD; 6.0±33.3 years). Seven patients (3.5%) had positive skin prick test to soy protein. The mean value for the absolute eosinophilic count was 0.4x109/L. The median for the total serum IgE level was 50 IU/L. According to age, the highest percentage of soy protein sensitivity was elicited among patients less than 3 years (57.14%), followed by those between 3 to 6 years (28.5%) and those between 6 and 15 years (14.28%). A positive family history of atopy was recorded in 122 (61%) of all cases. In terms of gender, incidence of soya sensitivity was higher among males than females but with no statistical difference. Although the most common allergic manifestations of all studied patients were respiratory (83%), and atopic dermatitis (22.5%), yet positive SPT to soy proteins was elicited in 43% in allergic rhinitis cases, in 29% of asthma patients, in 14% of patients with combined asthma and allergic rhinitis, and 14.3% of patients having eczema. Conclusion Soy protein sensitization is not uncommon in children especially in those with atopic manifestations. Large scale studies are needed to evaluate the actual incidence of soy protein hypersensitivity in children.