From the publisher: "Background: The introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing understanding of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization. However, these events have not been organized in a sequence of related events that is plausible to result in sensitization, and useful to challenge current hypotheses. The aim of this manuscript was to collect and structure the current mechanistic understanding of sensitization induction to food proteins by applying the concept of adverse outcome pathway (AOP). Main body: The proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respiratory sensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell-cell interactions and tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use in testing and assessment of proteins for their sensitizing potential. Conclusion: The application of the AOP concept to structure mechanistic in vivo and in vitro knowledge has made it possible to identify a number of methods, each addressing a specific KE, that provide information about the food allergenic potential of new proteins. When applied in the context of an integrated strategy these methods may reduce, if not replace, current animal testing approaches. The proposed AOP will be shared at the www.aopwiki.org platform to expand the mechanistic data, improve the confidence in each of the proposed KE and key event relations (KERs), and allow for the identification of new, or refinement of established KE and KERs." Authors: Jolanda H. M. van BilsenEmail author, Edyta Sienkiewicz-Szłapka, Daniel Lozano-Ojalvo, Linette E. M. Willemsen, Celia M. Antunes, Elena Molina, Joost J. Smit, Barbara Wróblewska, Harry J. Wichers, Edward F. Knol, Gregory S. Ladics, Raymond H. H. Pieters, Sandra Denery-Papini, Yvonne M. Vissers, Simona L. Bavaro, Colette Larré, Kitty C. M. Verhoeckx and Erwin L. Roggen
LINK
From teh UU repository: "Background: Oral immunotherapy (OIT) is a promising therapeutic approach to treat food allergic patients. However, there are some concerns regarding its safety and long-term efficacy. The use of non-digestible oligosaccharides might improve OIT efficacy since they are known to directly modulate intestinal epithelial and immune cells in addition to acting as prebiotics. Aim: To investigate whether a diet supplemented with plant-derived fructo-oligosaccharides (FOS) supports the efficacy of OIT in a murine cow's milk allergy model and to elucidate the potential mechanisms involved. Methods: After oral sensitization to the cow's milk protein whey, female C3H/HeOuJ mice were fed either a control diet or a diet supplemented with FOS (1% w/w) and received OIT (10 mg whey) 5 days a week for 3 weeks by gavage. Intradermal (i.d.) and intragastric (i.g.) challenges were performed to measure acute allergic symptoms and mast cell degranulation. Blood and organs were collected to measure antibody levels and T cell and dendritic cell populations. Spleen-derived T cell fractions (whole spleen-and CD25-depleted) were transferred to naive recipient mice to confirm the involvement of regulatory T cells (Tregs) in allergy protection induced by OIT + FOS. Results: OIT + FOS decreased acute allergic symptoms and mast cell degranulation upon challenge and prevented the challenge-induced increase in whey-specific IgE as observed in sensitized mice. Early induction of Tregs in the mesenteric lymph nodes (MLN) of OIT + FOS mice coincided with reduced T cell responsiveness in splenocyte cultures. CD25 depletion in OIT + FOS-derived splenocyte suspensions prior to transfer abolished protection against signs of anaphylaxis in recipients. OIT + FOS increased serum galectin-9 levels. No differences in short-chain fatty acid (SCFA) levels in the cecum were observed between the treatment groups. Concisely, FOS supplementation significantly improved OIT in the acute allergic skin response, %Foxp3+ Tregs and %LAP+ Th3 cells in MLN, and serum galectin-9 levels. Conclusion: FOS supplementation improved the efficacy of OIT in cow's milk allergic mice. Increased levels of Tregs in the MLN and abolished protection against signs of anaphylaxis upon transfer of CD25-depleted cell fractions, suggest a role for Foxp3+ Tregs in the protective effect of OIT + FOS. "
LINK
Chronic itching is a serious and uncomfortable condition. The scratch response might result in a vicious cycle of alternating itching and scratching. To develop psychological interventions for people suffering from chronic itching and to break the vicious itch-scratching-itch cycle, it is important to elucidate which environmental factors trigger itch sensations. Virtual reality (VR) techniques provide a useful tool to examine specific content characteristics in a three-dimensional (3D VR) environment and their influences on itch sensations and scratching behaviour. This article describes two experiments in which we focused on the effects of environmental information on itching and scratching behaviour. Additionally, in the second experiment, we examined the influence of having a chronic skin condition on sensitivity to itch induction. We found evidence for the importance of the content of audio–visual materials for the effectiveness in inducing feelings of itch in the observers. In both experiments, we observed significantly higher levels of perceived itch in the itch-inducing conditions than in the control condition. Moreover, the results showed that elevated levels of perceived itch were associated with an increase in scratching behaviours, which was especially salient in the contagious itch condition, in which perceived itch was accompanied by a significant increase in the number of scratches. Experiment 2 additionally showed increased perceived itch levels in participants who reported having a chronic skin condition, reflecting higher sensitivity to itch-inducing audio–visual stimuli in this group than in participants without a chronic skin condition. Based on the results we concluded that directing attention towards itch- or scratch aspects of related information in the environment and to the consequences for one’s own skin are effective tools to induce itch sensations and scratching behaviour. This knowledge provides tools for developing novel strategies in advising and treating people suffering from chronic itching and breaking the vicious itch-scratching-itch cycle.
