Under homeostatic conditions, as well as in various diseases, leukocyte migration is a crucial issue for the immune system that is mainly organized through the activation of bone marrow-derived cells in various tissues. Immune cell trafficking is orchestrated by a family of small proteins called chemokines. Leukocytes express cell-surface receptors that bind to chemokines and trigger transendothelial migration. Most allergic diseases, such as asthma, rhinitis, food allergies, and atopic dermatitis, are generally classified by the tissue rather than the type of inflammation, making the chemokine/chemokine receptor system a key point of the immune response. Moreover, because small antagonists can easily block such receptors, various molecules have been developed to suppress the recruitment of immune cells during allergic reactions, representing potential new drugs for allergies. We review the chemokines and chemokine receptors that are important in asthma, food allergies, and atopic dermatitis and their respectively developed antagonists.
Significant efforts are necessary to introduce new dietary protein sources to feed a growing world population while maintaining food supply chain sustainability. Such a sustainable protein transition includes the use of highly modified proteins from side streams or the introduction of new protein sources that may lead to increased clinically relevant allergic sensitization. With food allergy being a major health problem of increasing concern, understanding the potential allergenicity of new or modified proteins is crucial to ensure public health protection. The best predictive risk assessment methods currently relied on are in vivo models, making the choice of endpoint parameters a key element in evaluating the sensitizing capacity of novel proteins. Here, we provide a comprehensive overview of the most frequently used in vivo and ex vivo endpoints in murine food allergy models, addressing their strengths and limitations for assessing sensitization risks. For optimal laboratory‐to‐laboratory reproducibility and reliable use of predictive tests for protein risk assessment, it is important that researchers maintain and apply the same relevant parameters and procedures. Thus, there is an urgent need for a consensus on key food allergy parameters to be applied in future food allergy research in synergy between both knowledge institutes and clinicians.
The treatment of pregnant and lactating mice with nondigestible GOS/inulin prebiotics promotes a long-term protective effect against food allergies in the offspring.
CD9 was recently identified as a marker of murine IL-10-competent regulatory B cells. Functional impairments or defects in CD9+ IL-10-secreting regulatory B cells are associated with enhanced asthma-like inflammation and airway hyperresponsiveness. In mouse models, all asthma-related features can be abrogated by CD9+ B cell adoptive transfer. We aimed herein to decipher the profiles, features, and molecular mechanisms of the regulatory properties of CD9+ B cells in human and mouse. The profile of CD9+ B cells was analyzed using blood from severe asthmatic patients and normal and asthmatic mice by flow cytometry. The regulatory effects of mouse CD9+ B cells on effector T cell death, cell cycle arrest, apoptosis, and mitochondrial depolarization were determined using yellow dye, propidium iodide, Annexin V, and JC-1 staining. MAPK phosphorylation was analyzed by western blotting. Patients with severe asthma and asthmatic mice both harbored less CD19+CD9+ B cells, although these cells displayed no defect in their capacity to induce T cell apoptosis. Molecular mechanisms of regulation of CD9+ B cells characterized in mouse showed that they induced effector T cell cycle arrest in sub G0/G1, leading to apoptosis in an IL-10-dependent manner. This process occurred through MAPK phosphorylation and activation of both the intrinsic and extrinsic pathways. This study characterizes the molecular mechanisms underlying the regulation of CD9+ B cells to induce effector T cell apoptosis in mice and humans via IL-10 secretion. Defects in CD9+ B cells in blood from patients with severe asthma reveal new insights into the lack of regulation of inflammation in these patients.
Altogether, Results indicate that industrial processes such as deamidation or hydrolysis influences food allergenicity through immune modulation and helps us to develop tools to determine how these processes can influence this reaction and encourage or decrease allergic reactions.
Scope: Personal care products containing hydrolyzed gluten have been linked to spontaneous sensitization through the skin, however the impact of the hydrolysate characteristics on the sensitizing capacity is generally unknown. Methods and Results: The physicochemical properties of five different wheat-derived gluten products (one unmodified, one enzyme hydrolyzed, and three acid hydrolyzed) are investigated, and the skin sensitizing capacity is determined in allergy-prone Brown Norway rats. Acid hydrolyzed gluten products exhibited the strongest intrinsic sensitizing capacity via the skin. All hydrolyzed gluten products induced cross-reactivity to unmodified gluten in the absence of oral tolerance to wheat, but were unable to break tolerance in animals on a wheat-containing diet. Still, the degree of deamidation in acid hydrolyzed products is associated with product-specific sensitization in wheat tolerant rats. Sensitization to acid hydrolyzed gluten products is associated with a more diverse IgE reactivity profile to unmodified gluten proteins compared to sensitization induced by unmodified gluten or enzyme hydrolyzed gluten. Conclusion: Acid hydrolysis enhances the skin sensitizing capacity of gluten and drives IgE reactivity to more gluten proteins. This property of acid hydrolyzed gluten may be related to the degree of product deamidation, and could be a strong trigger of wheat allergy in susceptible individuals.
Heated foods are recommended for avoiding sensitization to food proteins, but depending on the physicochemical conditions during heating, more or less unfolded proteins aggregate differently. Whether the aggregation process could modulate allergenicity was investigated. Heating ovalbumin in opposite electrostatic conditions led to small (A-s, about 50 nm) and large (A-L, about 65 μm) aggregates that were used to sensitize mice. The symptoms upon oral challenge and rat basophil leukemia degranulation with native ovalbumin differed on the basis of which aggregates were used during the sensitization. Immunoglobulin-E (IgE) production was significantly lower with A-s than with A-L. Although two common linear IgE-epitopes were found, the aggregates bound and cross-linked IgE similarly or differently, depending on the sensitizing aggregate. The ovalbumin aggregates thus displayed a lower allergenic potential when formed under repulsive rather than nonrepulsive electrostatic conditions. This further demonstrates that food structure modulates the immune response during the sensitization phase with some effects on the elicitation phase of an allergic reaction and argues for the need to characterize the aggregation state of allergens.
Taken together, our results demonstrated a crucial role of the T-cell homing receptor CCR9 in this model and validated its potential for use in the development of therapeutic strategies for allergic diseases.
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