Development Of Food Allergy Research Articles

Propionibacterium freudenreichii Prevents Food Allergy in Mice via the Surface Layer Protein SlpB.

The prevalence of food allergies has increased in recent decades in industrialized developed countries. Defects are influenced by environmental factors in early life, including early colonizers of the human gut microbiota. Therapeutic solutions are limited, and the lack of efficient treatments has led to the search for new treatments, including biotherapies. Promising results from this search suggest that immunomodulatory probiotic bacteria, in particular, may yield new biotherapeutic or preventive strategies to address the increasing burden of food allergies. In this context, we investigated the potential impact of Propionibacterium freudenreichii CIRM-BIA129, a recognized immunomodulatory probiotic bacterium, on food allergy development in a murine model. Preventive effects of this probiotic were evaluated in the context of an induced wheat gliadin allergy. Following sensitization using gliadins, clinical and immunological parameters were monitored following an oral challenge with wheat gliadin. When consumed orally, P. freudenreichii CIRM-BIA129 prevented induced wheat gliadin allergy. Probiotic administration favored the differentiation of Treg cells at the expense of Th2 cells in mice. Notably, P. freudenreichii CIRM-BIA129 ΔslpB, which contains a mutation in the slpB gene encoding a key surface protein involved in adhesion and immunomodulation, failed to induce the same phenotype. Accordingly, the wild-type probiotic stimulated IL-10 production by human peripheral blood mononuclear cells, while the mutant did not. Altogether, these results indicate that the P. freudenreichii CIRM-BIA129 strain can mitigate the food allergic response through its immunomodulatory effects mediated by the surface layer protein SlpB. This finding provides new perspectives for biotherapies aimed at managing the increased prevalence of food allergy.

The impact of infant feeding practices on the risk of developing food allergies

The impact of infant feeding practices on the risk of developing food allergies

Risk factors and temporal associations of progression of the atopic march in children with early-onset atopic dermatitis

BackgroundRisk factors and the temporal relationship between atopic dermatitis (AD) and atopic march remain understudied. ObjectiveDetermine risk factors for atopic march in early-onset AD patients and the temporality between AD and atopic march. MethodsWe used the MarketScan Research Database for our retrospective cohort analysis from 2010-2018, comparing infants diagnosed with AD before age 1 with controls without early-onset AD. Primary outcomes were hazard ratios (HR) for development of asthma, allergic rhinitis and food allergy. ResultsCompared to 55,174 controls, higher proportions of the 27,228 AD patients developed asthma (19.21% vs 8.65%, p<0.001), allergic rhinitis (28.27% vs 12.62%, p<0.001), food allergy (16.00% vs 2.27%, p<0.001), and all atopic triad conditions (10.69% vs 0.71%, p<0.001). Among AD patients, higher proportions developed the atopic triad if they were male (HR 1.66, 95% confidence interval [1.45-1.90]), had severe disease (HR 3.16, [2.77-3.60]), or had family atopy history (HR>3.40, p<0.001 for all comparisons). Among AD patients, 20.1% developed allergic rhinitis. LimitationsOur study was based on health care claims data. ConclusionEarly-onset AD is associated with higher rates of developing atopic march conditions compared to controls. Particular attention should be paid towards risk factors and atopic march screening in early-onset AD patients.

Long-term health outcomes of children born by cesarean section: A nationwide population-based retrospective cohort study in Taiwan

BackgroundTaiwan had high cesarean rate which exceeded the recommended threshold (15%), set by WHO. However, there have not a comprehensive study to discuss the long-term offspring consequences of cesarean section (CS). This study aimed to show whether allergy disorders, obesity and respiratory infection of children are associated with modes of delivery, using the National Health Insurance Research Database (NHIRD) of Taiwan. MethodsThis study used the maternal and child health database of NHIRD. We included the children who birth between 2004 and 2013 and inter-linked the database of the mother and children. The participants were followed until 2018/12/31. We performed a Cox proportional hazards model to identify the association of CS with respiratory tract infection, allergy disorder, and obesity diagnosed in childhood. ResultsCS significantly increased the risk of developed childhood asthma (adjusted hazard ratio [aHR] = 1.03; 95% confidence interval [CI]: 1.02–1.03), allergy rhinitis (aHR = 1.04; 95% CI: 1.04–1.05), atopic dermatitis (aHR = 1.05; 95% CI: 1.04–1.06), respiratory tract infection (aHR = 1.07; 95% CI: 1.06–1.07) and overweight (aHR = 1.29; 95% CI: 1.18–1.40) even after adjusting with confounding factor. Development of food allergy (aHR = 1.13; 95% CI: 0.87–1.47) was not associated with cesarean section. ConclusionThis study indicated that children delivered by CS more commonly developed respiratory tract infections, asthma, allergic rhinitis, atopic dermatitis, obesity than children delivered vaginally. Among these, obesity have a stronger association with cesarean section.

Impact of ovalbumin allergy on oral and gut microbiome dynamics in 6-week-old BALB/c mice.

The gut microbiota is known to have a significant impact on the development of food allergy, and several recent studies have suggested that both oral microbiota, which first come into contact with allergenic foods, may have a profound influence on the development of food allergy. In this study, we have established an ovalbumin-sensitive mice model by utilizing ovalbumin as a sensitizing agent. Subsequently, we performed a comprehensive analysis of the gut and oral microbiota in ovalbumin-sensitive mice and the control mice using full-length 16S rRNA sequencing analysis. Interestingly, both the gut and oral microbiota of ovalbumin-sensitized mice exhibited significant dysbiosis. The relative abundance of s__Lactobacillus_intestinalis in the gut microbiota of ovalbumin-sensitive mice exhibited a significant decrease, whereas the abundance of s__Agrobacterium_radiobacter and s__Acinetobacter_sp__CIP_56_2 displayed a significant increase. Furthermore, the relative abundance of s__unclassified_g__Staphylococcus, s__Streptococcus_hyointestinalis, and s__unclassified_g__Dechloromonas in the oral microbiota of ovalbumin-sensitive mice revealed a significant decrease. In contrast, the abundance of 63 other species, including s__Proteiniclasticum_ruminis, s__Guggenheimella_bovis, and s__Romboutsia_timonensis, demonstrated a significant increase. The random forest classifier achieved the best accuracy in predicting the outcome of food allergy using three gut and three oral biomarkers, with accuracies of 94.12 and 100%, respectively. Based on the predictions of the PICRUSt2 analysis, the only consistent finding observed across multiple samples from both the groups of mice was a significant up-regulation of the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway in the ovalbumin-sensitized mice. Our study demonstrates that ovalbumin-sensitized mice experience substantial alterations in both gut and oral microbial composition and structure, and specific strains identified in this study may serve as potential biomarkers for food allergy screening. Moreover, our findings highlight that the oral environment, under the same experimental conditions, exhibited greater precision in detecting a larger number of species. Additionally, it is worth noting that the NOD-like receptor signaling pathway plays a vital role in the pathogenesis of OVA (ovalbumin)-induced allergy. These findings will generate novel concepts and strategies in the realm of food allergy prevention and treatment.

Progressive accumulation of hyperinflammatory NKG2Dlow NK cells in early childhood severe atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that often precedes the development of food allergy, asthma, and allergic rhinitis. The prevailing paradigm holds that a reduced frequency and function of natural killer (NK) cell contributes to AD pathogenesis, yet the underlying mechanisms and contributions of NK cells to allergic comorbidities remain ill-defined. Here, analysis of circulating NK cells in a longitudinal early life cohort of children with AD revealed a progressive accumulation of NK cells with low expression of the activating receptor NKG2D, which was linked to more severe AD and sensitivity to allergens. This was most notable in children co-sensitized to food and aeroallergens, a risk factor for development of asthma. Individual-level longitudinal analysis in a subset of children revealed coincident reduction of NKG2D on NK cells with acquired or persistent sensitization, and this was associated with impaired skin barrier function assessed by transepidermal water loss. Low expression of NKG2D on NK cells was paradoxically associated with depressed cytolytic function but exaggerated release of the proinflammatory cytokine tumor necrosis factor-α. These observations provide important insights into a potential mechanism underlying the development of allergic comorbidity in early life in children with AD, which involves altered NK cell functional responses, and define an endotype of severe AD.

Innate lymphoid cells in immunoglobulin E-mediated food allergy.

Recognition of the importance of innate lymphoid cells (ILCs) in the immune mechanisms of food allergy has grown in recent years. This review summarizes recent findings of ILCs in immunoglobulin E (IgE)-mediated food allergy. New research on ILCs in the context of the microbiome and other atopic diseases are also considered with respect to how they can inform understanding of the role of ILCs in food allergy. ILCs can mediate allergic and tolerogenic responses through multiple pathways. A novel subset of interleukin (IL)-10 producing ILC2s are associated with tolerance following immunotherapy to grass pollen, house dust mite allergy and lipid transfer protein allergy. ILC2s can drive food allergen-specific T cell responses in an antigen-specific manner. A memory subset of ILC2s has been identified through studies of other atopic diseases and is associated with effectiveness of response to therapy. The role of ILCs in food allergy and oral tolerance is relatively understudied compared to other diseases. ILCs can modulate immune responses through several mechanisms, and it is likely that these are of importance in the context of food allergy. Better understanding of theses pathways may help to answer fundamental questions regarding the development of food allergy and lead to novel therapeutic targets and treatment.

Marine Bioactive Compounds with Functional Role in Immunity and Food Allergy.

Food allergy, referred to as the atypical physiological overreaction of the immune system after exposure to specific food components, is considered one of the major concerns in food safety. The prevalence of this emerging worldwide problem has been increasing during the last decades, especially in industrialized countries, being estimated to affect 6-8% of young children and about 2-4% of adults. Marine organisms are an important source of bioactive substances with the potential to functionally improve the immune system, reduce food allergy sensitization and development, and even have an anti-allergic action in food allergy. The present investigation aims to be a comprehensive report of marine bioactive compounds with verified actions to improve food allergy and identified mechanisms of actions rather than be an exhaustive compilation of all investigations searching beneficial effects of marine compounds in FA. Particularly, this research highlights the capacity of bioactive components extracted from marine microbial, animal, algae, and microalgae sources, such as n-3 long-chain polyunsaturated fatty acids (LC-PUFA), polysaccharide, oligosaccharide, chondroitin, vitamin D, peptides, pigments, and polyphenols, to regulate the immune system, epigenetic regulation, inflammation, and gut dysbiosis that are essential factors in the sensitization and effector phases of food allergy. In conclusion, the marine ecosystem is an excellent source to provide foods with the capacity to improve the hypersensitivity induced against specific food allergens and also bioactive compounds with a potential pharmacological aptitude to be applied as anti-allergenic in food allergy.

Cord blood methylation at TNFRSF17 is associated with early allergic phenotypes

Food allergy and eczema are the earliest allergic phenotypes in childhood. These diseases could be related to either IgE-mediated or non-IgE-mediated reactions to the allergen. TNFRSF17 is a key molecule in B cell maturation and is important in both types of responses.We conducted a study comparing the relative expression and the methylation status at the TNFRSF17 in regard to the child’s early atopic sensitisation and allergic phenotypes.In the recruited population of 200 women and 174 children with available clinical data (physical examination by allergist and antigen-specific IgE measurements), 78 cord blood samples were included in the gene expression analysis (relative gene expression with GAPDH as reference by RT-PCR) and 96 samples with microarray DNA methylation data (whole genome methylation profile Infinium MethylationEPIC).The altered TNFRSF17 methylation pattern in the cord blood at both single cg04453550 and mean methylation at upstream of TNFRSF17 was observed in children who developed food allergy and/or eczema in early childhood. The change in methylation profile was mirrored by the relative expression. The profile of IgE sensitisation to food and/or inhalant allergens was not significantly associated with either methylation or expression of TNFRSF17.In conclusion, methylation at the upstream sites at TNFRSF17 in the cord blood at birth is associated with food allergy and eczema early in childhood.

Assessing the Potential Diagnostic Value of Indonesian Local Allergen Skin Prick Testing (SPT) for Cow’s Milk Allergy among Atopic Dermatitis Patients

Background: Atopic dermatitis (AD) is a multifactorial chronic, frequently recurrent, inflammatory skin condition. The development of IgE-mediated food allergies and food sensitivity are both associated with atopic dermatitis. Cow’s milk allergy (CMA) caused the most common hypersensitivity reaction during childhood; however, the prevalence in adults is around 0.5%. Patients with AD use the Skin Prick Test (SPT) to evaluate the specific sensitization process. Purpose: This study aimed to assess cow's milk allergy among adult AD patients using local allergen extract SPT, standard SPT, and specific IgE (sIgE), as well as evaluating the conformity and relevance of the test results. Methods: Using consecutive sampling technique, the study was conducted twice on 45 adult AD patients with a one-week interval between administrations. Result: Local cow's milk SPT showed 4 positive results, and standard SPT showed 5. No sIgE test was positive. Local SPT was negative for 86.67% of individuals without a history of suspected cow's milk allergies. Standard SPT results were positive for 2.22% of individuals with a history of suspected cow's milk allergies and negative for 86.67% of those without. The relevance between local and standard SPT was shown to be substantial (k = 0.384, p = 0.000). Conclusion: The result of the local cow’s milk SPT and the patient’s history had good conformity, and the relevance with standard SPT was significant in diagnosing cow’s milk allergy among AD patients.

Mechanisms for initiation of food allergy by skin pre-disposed to atopic dermatitis.

Food allergy can be life-threatening and often develops early in life. In infants and children, loss-of-function mutations in skin barrier genes associate with food allergy. In a mouse model with skin barrier mutations (Flakey Tail, FT+/- mice), topical epicutaneous sensitization to a food allergen peanut extract (PNE), an environmental allergen Alternaria alternata (Alt) and a detergent induce food allergy and then an oral PNE-challenge induces anaphylaxis. Exposures to these allergens and detergents can occur for infants and children in a household setting. From the clinical and preclinical studies of neonates and children with skin barrier mutations, early oral exposure to allergenic foods before skin sensitization may induce tolerance to food allergens and thus protect against development of food allergy. In the FT+/- mice, oral food allergen prior to skin sensitization induce tolerance to food allergens. However, when the skin of FT+/- pups are exposed to a ubiquitous environmental allergen at the time of oral consumption of food allergens, this blocks the induction of tolerance to the food allergen and the mice can then be skin sensitized with the food allergen. The development of food allergy in neonatal FT+/- mice is mediated by altered skin responses to allergens with increases in skin expression of interleukin 33, oncostatin M and amphiregulin. The development of neonate food allergy is enhanced when born to an allergic mother, but it is inhibited by maternal supplementation with α-tocopherol. Moreover, preclinical studies suggest that food allergen skin sensitization can occur before manifestation of clinical features of atopic dermatitis. Thus, these parameters may impact design of clinical studies for food allergy, when stratifying individuals by loss of skin barrier function or maternal atopy before offspring development of atopic dermatitis.

Prevalence and Determinants of Food Allergy in the Era of Early Allergen Introduction: The EarlyNuts Population-Based Study

BackgroundInfant feeding guidelines in Australia changed in 2016 to recommend introduction of common allergy causing foods by age 1 year to prevent food allergy. Although the majority of Australian infants now eat peanut and egg by age 6-months, some still develop food allergy despite introducing allergens early. ObjectiveWe aimed to describe the prevalence of food allergy in a cohort recruited after introducing the nation-wide allergy prevention recommendations; identify characteristics of infants who developed allergy despite early introduction of allergens; and estimate the causal effect of modifiable exposures on food allergy prevalence and whether this differed between infants who were introduced to allergen before or after age 6 months. MethodsWe recruited a population-based sample of 12-month-old infants in Melbourne, Australia. Infants had skin prick tests to 4 foods and parents completed questionnaires. Infants with evidence of sensitisation were offered oral food challenges. Prevalence estimates were adjusted using inverse probability weighting. ResultsIn a cohort of infants (n=1420) where nearly all infants had been introduced to common allergens such as egg, milk and peanut by one-year-of age, the prevalence of food allergy remained high at 11.3% (95% CI 9.6-13.4%). Infants who developed food allergy despite introducing the allergen by age 6-months were more likely to have Asian-born parents. Early-onset moderate/severe eczema was associated with an increased odds of food allergy, irrespective of whether allergens were introduced before or after age 6 months. Among infants who were introduced to peanut ≤6m, antibiotic use by age 6 months was associated with an increased odds of peanut allergy (aOR 6.03 (95%CI 1.15-31.60). ConclusionIn a cohort where early allergen introduction was common, the prevalence of food allergy remained high. Infants who developed food allergy despite introducing the respective allergen by 6 months were more likely to have Asian parents and early-onset eczema. New interventions are needed for infants with a phenotype of food allergy that is not amenable to early allergen introduction.

Skin Predictive Biomarkers for the Development of Atopic Dermatitis and Food Allergy in Infants.

The pathogenesis of atopic dermatitis (AD) is multifactorial, involving a dynamic interplay between genetic susceptibility, skin-barrier dysfunction, microbiome alterations, and immune dysregulation, whereas food allergy (FA) arises from the interplay of transcutaneous sensitization to food allergens and failure in the induction of oral tolerance. Skin epicutaneous sensitization is commonly involved in the development of AD and FA. Although clinical trials have been conducted to prevent AD or FA by applications of emollients on the skin after birth, the results are not consistent. For more effective preventive strategies, reliable biomarkers are required to identify high-risk individuals. Skin tape stripping (STS) is a non-invasive technique for identifying these biomarkers in the skin. By analyzing the stratum corneum collected via STS, researchers can gain molecular or cellular insights into the early pathogenesis and potential progression of AD and FA. This review aims to elucidate the critical aspects of AD and FA, underlying their pathogenesis, early manifestations, and STS's potential as a tool for identifying predictive non-invasive biomarkers in infants prior to onset of clinical disease.

Association between frozen embryo transfer and childhood allergy: a retrospective cohort study

Research questionDoes frozen embryo transfer (FET) elevate the risk of allergic diseases in offspring? DesignIn this study, we followed up 653 singleton children, including 166 children born through FET and 487 children born through natural conception (NC). Demographic characteristics, perinatal information and allergic diseases of children and their parents were collected through clinical medical systems and questionnaires. Furthermore, among these 653 children, allergen-specific IgE testing was performed using peripheral blood samples collected from 207 children, including 62 children in the NC group and 145 children in the FET group. The prevalence rates of allergic diseases and the positive rates of allergen-specific IgE testing were compared between FET and NC groups with adjustments for confounding factors. ResultsResults showed that children born from FET had a significantly elevated prevalence rate of food allergy (aOR=3.154, 95% CI:1.895-5.250, p<0.001). Align with this, the positive rates of food allergen sensitization were also increased (aOR=5.767, 95%CI: 2.859-11.751, p<0.001). In addition, FET children exhibited a higher positive sensitization rate to at least one allergen compared to NC children (aOR=3.127, 95%CI: 1.640-5.961, p<0.001). No association was observed between FET and other allergic diseases, including asthma (p=0.136), atopic dermatitis (AD) (p=0.130) and allergic rhinitis (AR) (p=0.922). Also, allergen-sensitization IgE testing indicated no differences between FET and NC children in the positive rates of other common allergens, including animals and insects allergens (p=0.627), inhaled outdoor allergens (p=0.915), and inhaled outdoor allergens (p=0.544). ConclusionOur study suggested that children born from FET had an increased risk of developing food allergies in early childhood.

Novel strategies for predicting allergenicity: development of a ranking method and screening tools to assess the allergy risk of innovative proteins

Abstract To protect individuals who already have or are at risk of developing immune‐mediated adverse reactions to food, novel foods and genetically modified organisms (GMOs) undergo an allergenicity risk assessment. There are shortcomings in this process that could be improved through use of well‐defined clinically relevant allergen molecules with different allergenic potential. The objective of this project was to develop novel strategies for predicting allergenicity of innovative/novel proteins that address this issue. We undertook a systematic review of allergen molecules in foods listed on Annex II of the Food Information for Consumers Regulation together with additional foods known to cause IgE‐mediated food allergies in at least one European region with a prevalence of 0.5%. Around 750 in‐scope papers were quality assessed to allow clinical relevance of allergen molecules to be ranked. The best characterised clinically relevant allergens were identified in peanut, hazelnut, cow's milk, fish and crustacean shellfish with data lacking for allergens from foods such as pecan, Macadamia, lupin and melon. Furthermore, an assessment of in silico tools allergenicity prediction found that, whilst many were able to correctly predict allergenicity, none were able to provide an output that could be linked to the clinical relevance. Building on these outcomes an approach for allergenicity risk assessment has been developed that brings together elements of exposure assessment, combining in silico, in vitro, and in vivo methods. Tools for assessment of risks of cross‐reactive allergies are more mature and only require refinement to improve the outputs to inform the allergenicity risk assessment process. However, as mechanisms underlying development of food allergy are not fully elucidated, and remain a matter of ongoing research, prediction of de novo sensitisation is uncertain.

Maternal and Infant Dietary Patterns Are Not Related to Food Allergy Risk in Singapore Children: GUSTO Cohort Study

BackgroundWe previously reported that delayed allergenic food introduction in infancy did not increase food allergy risk until age 4 y within our prospective cohort. However, it remains unclear whether other aspects of maternal or infant diet play roles in the development of childhood food allergy. ObjectivesWe examined the relationship between maternal pregnancy and infant dietary patterns and the development of food allergies until age 8 y. MethodsAmong 1152 Singapore Growing Up in Singapore Towards healthy Outcomes study mother–infant dyads, the infant’s diet was ascertained using food frequency questionnaires at 18 mo. Maternal dietary patterns during pregnancy were derived from 24-h diet recalls. Food allergy was determined through interviewer-administered questionnaires at regular time points from infancy to age 8 y and defined as a positive history of allergic reactions, alongside skin prick tests at 18 mo, 3, 5, and 8 y. ResultsFood allergy prevalence was 2.5% (22/883) at 12 mo and generally decreased over time by 8 y (1.9%; 14/736). Higher maternal dietary quality was associated with increased risk of food allergy (P ≤ 0.016); however, odds ratios were modest. Offspring food allergy risk ≤8 y showed no associations with measures of infant diet including timing of solids/food introduction (adjusted odds ratio [aOR]: 0.90; 95% confidence interval [CI]: 0.42, 1.92), infant’s diet quality (aOR: 0.93; 95% CI: 0.88, 0.99) or diet diversity (aOR: 0.84; 95% CI: 0.6, 1.19). Most infants (89%) were first introduced to cow milk protein within the first month of life, while egg and peanut introduction were delayed (58.3% introduced by mean age 8.8 mo and 59.8% by mean age 18.1 mo, respectively). ConclusionsApart from maternal diet quality showing a modest association, infant’s allergenic food introduction, diet quality, and dietary diversity were not associated with food allergy development in this Asian pediatric population. Interventional studies are needed to evaluate the efficacy of these approaches to food allergy prevention across different populations.

Disorders of the small intestinal microenvironment in ovalbumin-sensitized mice and mitigation strategies of 2′-fucosyllactose and Bifidobacterium longum subsp. Infantis

The small intestine is responsible for approximately 90% of nutrient absorption, and it is widely believed that food allergens primarily sensitize through the small intestine. No study to date has investigated the association between food allergy (FA) and the altered small intestinal microenvironment (SIM), which would help to understand the biological process linking FA, and could provide new insights into the nutritional modulation of FA. In this study, we aimed to investigate the association between the development of FA and the altered SIM in ovalbumin-sensitized mice, as well as elucidate the underlying mechanisms by which Bifidobacterium longum subsp. Infantis (B. infantis) and/or 2′-fucosyllactose regulate allergenic reactions from the perspective of SIM. Our findings demonstrate that ovalbumin-induced disruption of SIM is characterized by increased bacteria diversity, dysregulated production of organic acids and amino acids, elevated ileal pH levels, and disrupted intestinal tight junctions. Furthermore, B. infantis and 2′-fucosyllactose cotreatment most significantly repaired ovalbumin sensitization-induced SIM dysbiosis compared to mono-treatment with either B. infantis or 2′-fucosyllactose alone. Additionally, impaired intestinal barrier function may impact lung homeostasis by influencing material exchange between the lumen and tissues, thereby increasing susceptibility to pulmonary. Notably, B. infantis and/or 2′-fucosyllactose differentially regulated both SIM and lung homeostasis. The present study supports the notion that disrupted small intestinal microenvironment homeostasis underlie the development of food allergy and highlights the significance of the small intestine-lung axis as a target for probiotic and/or prebiotic-mediated modulation of food allergy.

Mechanisms of TFR cell-mediated regulation of microbiota-reactive IgA responses

Abstract The rising prevalence of food allergies impacting over 10% of the U.S. population requires innovative diagnostic approaches and therapeutic interventions. Gut microbiota alterations play a crucial role in food allergy development, with immunoglobulin IgA (IgA) actively regulating gut microbiome composition. While T follicular helper (TFH) cells aid in high-affinity antigen-specific IgA production, T follicular regulatory (TFR) cells' role in generating microbiota-specific IgA remains unclear. Using a unique TFR cell-deficient mouse model (Bcl6FC) and flow cytometry staining, we found increased fecal IgA-coated bacteria over time in Bcl6FC compared to WT mice after sensitization. IgA-seq revealed differential baseline microbiota IgA-coating in naïve Bcl6FC, displaying increased alpha diversity and more taxa with higher relative abundance than WT mice. Calculating the IgA-index demonstrated elevated IgA binding in Bcl6FC mice to specific taxa, primarily Firmicute members, indicating TFR cells' suppression of taxon-specific IgA in the peanut allergy model. Ongoing experiments, including the adoptive transfer of WT TFR cells into Bcl6FC mice and the assessment of IgA-coated biome function via Fecal Microbiota Transplantation (FMT) into germ-free mice in a peanut allergy model, aim to validate TFR cells' role in generating microbiota-specific IgA responses. This contributes essential insights for potential therapeutic antibodies targeting specific commensals.

Skin-centered strategies in food allergy prevention.

While the early introduction of food allergens in the infant diet has been shown to be effective at preventing the development of food allergy (FA), its implementation in real life has been associated with various challenges. Interventions aimed at correcting skin barrier dysfunction have been explored in recent decades as a distinct or complementary mean to prevent allergic sensitization through the skin and subsequent development of FA. Studies assessing the application of emollient from birth have yielded conflicting results, and meta-analyses have demonstrated either no effect or only a slight positive effect on FA prevention. However, a careful review of the clinical trials reveals that different emollients were used, which may have explained some of the discrepancies between study results. Emollient application protocols also varied widely between studies. While firm conclusions cannot be drawn with regard to their overall efficacy at preventing FA, the available data provide valuable insight into the characteristics that could be associated with a more effective intervention. Namely, successful trials tended to use emollients with an acidic pH of 5.5, applied over the entire body, and combined with topical corticosteroids in affected areas. Consensus on the optimal strategy to restore skin barrier function could help improve the homogeneity and clinical relevance of future trials on this topic. In the meantime, clinicians should avoid products associated with worse outcomes.

Group 2 innate lymphoid cells are key in lipid transfer protein allergy pathogenesis.

Immunopathology in food allergy is characterized by an uncontrolled type 2 immune response and specific-IgE production. Recent studies have determined that group 2 innate lymphoid cells (ILC2) participate in the food allergy pathogenic mechanism and their severity. Our objective was to investigate the role of ILC2 in peach-allergic patients due to non-specific lipid transfer protein (Pru p 3) sensitization. The immune response in peripheral blood mononuclear cells was characterized in lipid transfer protein-allergic patients and healthy controls. We have analyzed the Pru p 3 uptake on ILC2, the expression of costimulatory molecules, and their involvement on the T-cell proliferative response and cytokine production under different experimental conditions: cytokines involved in group 2 innate lymphoid cell activation (IL-33 and IL-25), Pru p 3 as main food allergen, and the combination of both components (IL-33/IL-25+Pru p 3) using cell sorting, EliSpot, flow cytometry, and confocal microscopy. Our results show that Pru p 3 allergen is taken up by group 2 innate lymphoid cells, regulating their costimulatory molecule expression (CD83 and HLA-DR) depending on the presence of Pru p 3 and its combination with IL-33/IL-25. The Pru p 3-stimulated ILC2 induced specific GATA3+Th2 proliferation and cytokine (IL-4, IL-5, and IL-13) production in lipid transfer protein-allergic patients in a cell contact-dependent manner with no changes in Tbet+Th1- and FOXP3+Treg cell differentiation. The results indicate that in lipid transfer protein-allergic patients, the responsible allergen, Pru p 3, interacts with group 2 innate lymphoid cells, promoting a Th2 cell response. Our results might be of interest in vivo, as they show a role of group 2 innate lymphoid cells as antigen-presenting cells, contributing to the development of food allergy. Consequently, group 2 innate lymphoid cells may be considered as potential therapeutic targets.