Dietary Antigens Research Articles

Strain-specific differences in reovirus infection of murine macrophages segregate with polymorphisms in viral outer-capsid protein σ3.

Mammalian orthoreovirus (reovirus) strains type 1 Lang (T1L) and type 3 Dearing-RV (T3D-RV) infect the intestine in mice but differ in the induction of inflammatory responses. T1L infection is associated with the blockade of oral immunological tolerance to newly introduced dietary antigens, whereas T3D-RV is not. T1L infection leads to an increase in infiltrating phagocytes, including macrophages, in gut-associated lymphoid tissues that are not observed in T3D-RV infection. However, the function of macrophages in reovirus intestinal infection is unknown. Using cells sorted from infected intestinal tissue and primary cultures of bone-marrow-derived macrophages (BMDMs), we discovered that T1L infects macrophages more efficiently than T3D-RV. Analysis of T1L × T3D-RV reassortant viruses revealed that the viral S4 gene segment, which encodes outer-capsid protein σ3, is responsible for strain-specific differences in infection of BMDMs. Differences in the binding of T1L and T3D-RV to BMDMs also segregated with the σ3-encoding S4 gene. Paired immunoglobulin-like receptor B (PirB), which serves as a receptor for reovirus, is expressed on macrophages and engages σ3. We found that PirB-specific antibody blocks T1L binding to BMDMs and that T1L binding to PirB-/- BMDMs is significantly diminished. Collectively, our data suggest that reovirus T1L infection of macrophages is dependent on engagement of PirB by viral outer-capsid protein σ3. These findings raise the possibility that macrophages function in the innate immune response to reovirus infection that blocks immunological tolerance to new food antigens.IMPORTANCEMammalian orthoreovirus (reovirus) infects humans throughout their lifespan and has been linked to celiac disease (CeD). CeD is caused by a loss of oral immunological tolerance (LOT) to dietary gluten and leads to intestinal inflammation following gluten ingestion, which worsens with prolonged exposure and can cause malnutrition. There are limited treatment options for CeD. While there are genetic risk factors associated with the illness, triggers for disease onset are not completely understood. Enteric viruses, including reovirus, have been linked to CeD induction. We found that a reovirus strain associated with oral immunological tolerance blockade infects macrophages by virtue of its capacity to bind macrophage receptor PirB. These data contribute to an understanding of the innate immune response elicited by reovirus, which may shed light on how viruses trigger LOT and inform the development of CeD vaccines and therapeutic agents.

Ovalbumin-induced food allergy suppression via regulatory T cell expansion mediated by a TNFR2 agonist in mice

Food allergies represent a growing health concern worldwide, characterized by abnormal immune responses to specific dietary antigens. This condition is often associated with a dysregulation of immune tolerance, especially within the intestinal mucosa. Regulatory T cells (Tregs), a crucial subset of lymphocytes, play a central role in maintaining peripheral immune tolerance and are abundant in the intestinal lamina propria. Recent studies have highlighted Treg dysfunction in patients with food allergies, suggesting a potential connection between impaired Treg function and allergy onset. Therefore, strategies to adequately control and activate Tregs could offer new avenues for the prevention and treatment of food allergies. Our research focuses on targeting the regulatory molecule, tumor necrosis factor receptor type 2 (TNFR2), a key modulator of Treg function. We have developed a TNFR2 agonist, scR2agoTNF-Fc, characterized by high TNFR2-stimulating activity and enhanced blood retention in vivo for Treg expansion. In this study, we utilized an ovalbumin (OVA)-induced food allergy mouse model to verify the therapeutic potential of scR2agoTNF-Fc in modulating allergic responses and restoring immune balance. The results showed that scR2agoTNF-Fc promoted the expansion of Treg population in vivo in mice. In addition, scR2agoTNF-Fc reduced diarrhea caused by the food allergy. This was consistent with the molecular mechanisms of suppression of blood immunoglobulins and Th2 cells. Therefore, it was shown that quantitative and functional enhancement of Tregs by the TNFR2 agonist, scR2agoTNF-Fc, may be effective in treating food allergies.

Fmo5 plays a sex-specific role in goblet cell maturation and mucus barrier formation.

The intestine plays a key role in metabolism, nutrient and water absorption, and provides both physical and immunological defense against dietary and luminal antigens. The protective mucosal lining in the intestine is a critical component of intestinal barrier that when compromised, can lead to increased permeability, a defining characteristic of inflammatory bowel disease (IBD), among other intestinal diseases. Here, we define a new role for the flavin-containing monooxygenase (FMO) family of enzymes in maintaining a healthy intestinal epithelium. Using Caenorhabditis elegans we measure intestinal barrier function, actin expression, and intestinal damage response. In mice, we utilize an intestine-specific, tamoxifen- inducible knockout model of the mammalian homolog of Cefmo-2 , Fmo5, and assess histology, mucus barrier thickness, and goblet cell physiology. We also treat mice with the ER chaperone Tauroursodeoxycholic acid (TUDCA). In nematodes, we find Cefmo-2 is necessary and sufficient for intestinal barrier function, intestinal actin expression, and is induced by intestinal damage. In mice, we find striking changes to the intestine within two weeks following Fmo5 disruption. Alterations include sex-dependent changes in colon epithelial histology, goblet cell localization, and mucus barrier formation. These changes are significantly more severe in female mice, mirroring differences observed in IBD patients. Furthermore, we find increased protein folding stress in Fmo5 knockout animals and successfully rescue the severe female phenotype with addition of a chemical ER chaperone. Together, our results identify a highly conserved and novel role for Fmo5 in the mammalian intestine and support a key role for Fmo5 in maintenance of ER/protein homeostasis and proper mucus barrier formation.

Pathogenic mechanisms in the evolution of food allergy.

The early development of the neonatal immune system is profoundly influenced by exposure to dietary and microbial antigens, which shapes mucosal tolerance. Successful oral tolerance induction is crucially dependent on microbially imprinted immune cells, most notably the RORγt+ regulatory T (Treg) and antigen presenting cells and is essential for preventing food allergy (FA). The development of FA can be envisioned to result from disruptions at key checkpoints (CKPTs) that govern oral tolerance induction. These include gut epithelial sensory and effector circuits that when dysregulated promote pro-allergic gut dysbiosis. They also include microbially imprinted immune regulatory circuits that are disrupted by dysbiosis and pro-allergic immune responses unleashed by the dysregulation of the aforementioned cascades. Understanding these checkpoints is essential for developing therapeutic strategies to restore immune homeostasis in FA.

Oral tolerance to dietary antigens and Foxp3+ regulatory T cells.

Immune tolerance to foods develops in the intestine upon food ingestion and is essential to prevent IgE-mediated food allergy and gut inflammation. In homeostasis, the intestine is a tolerogenic environment that favors the formation of food-specific Foxp3+ regulatory T cells. A tolerogenic intestinal environment depends on colonization by diverse microbiota and exposure to solid foods at a critical period in early life. These early immune responses lead to the induction of antigen-specific Foxp3+ regulatory T cells in draining mesenteric lymph nodes. These peripherally induced regulatory cells circulate and seed the lamina propria of the gut, exerting suppressive function systemically and locally in the intestine. Successful establishment of a tolerogenic intestinal environment in early life sets the stage for oral tolerance to new antigens in adult life.

Differential changes in mast cells with food reintroduction in children with Eosinophilic Esophagitis.

Intraepithelial mast cells (MC) are increased in Eosinophilic Esophagitis (EoE) and reduced with elimination of dietary antigens. Single food reintroduction can identify triggers of eosinophilia however it remains unknown the extent to which specific foods trigger intraepithelial mastocytosis. We hypothesized that specific foods drive different degrees of MC inflammation. We previously reported a prospective pediatric EoE cohort treated with a 4-food elimination diet (4FED) with removal of soy, egg, wheat, milk. We retrieved unstained slides in which baseline, 4FED, and post-4FED diet reintroduction time points were available. Slides were stained with tryptase, and intraepithelial MCs were counted. Comparisons were made by stratifying patients by eosinophilia, basal cell hyperplasia (BCH), endoscopic abnormalities, and symptoms. Pearson correlation was assessed for MCs with eosinophilic, endoscopic and BCH severity, symptoms, and a novel mucosal activity score (MAS) combining endoscopic and histologic structural severity. Slides were available from 37 patients with at least 1 food reintroduced. MCs were significantly reduced with 4FED. Wheat led to increased intraepithelial MCs in the upper esophagus and with food-induced eosinophilia, while milk led to significantly increased MCs in the upper and lower esophagus and was significantly associated with patients with food-triggered eosinophilia, endoscopic abnormalities, BCH, and symptoms. MCs best correlated with the MAS during milk reintroduction. In children with EoE, MCs are reduced with 4FED. During milk reintroduction, significant increases in MCs were observed with all metrics of inflammation along with moderate correlation with structural mucosal activity that was not seen with other foods. This suggests milk exerts unique effects either directly or indirectly on MCs in the esophagus in EoE patients.

Oral exposure to nano- and microplastics: Potential effects in food allergies?

BackgroundFood allergies (FA) is an inappropriate immune response to dietary antigens and ranks among the most common chronic diseases globally, with a rising incidence. Environmental exposure significantly influences the development of FA. In modern life, hundreds of thousands of novel environmental contaminants have been introduced, including nano- and microplastics (NMPs). The recently introduced ‘Epithelial Barrier Theory’ suggests that NMPs damage the epithelium of our skin, lungs and gastrointestinal system. And studies also have shown a correlation between NMPs exposure and allergic diseases, such as allergic asthma and rhinitis. However, the relationship between NMPs and FA remains unclear. There is a possibility that high concentrations of NMPs in the diet and environment could increase the prevalence or severity of FA. PurposeThis review aimed to provide relevant information on the possible effects of NMPs exposure on FA. Main findingsContaminating NMPs can interact with food allergens in the food matrix, potentially binding to and altering their structure. Moreover, NMPs might decrease the gastrointestinal digestibility of food allergens, increase intestinal permeability, promote an intestinal inflammatory environment in the intestines, cause intestinal dysbiosis or interfere with immune systems-all of which might enhance sensitivity to food allergens. Principal conclusionsGiven the limited information on the impacts of NMPs exposure regarding to the risk of FA development, further research is needed to determine whether NMPs could amplify the risk of allergic sensitization to food proteins.

Viral Vector Based Immunotherapy for Peanut Allergy.

Food allergy (FA) is estimated to impact up to 10% of the population and is a growing health concern. FA results from a failure in the mucosal immune system to establish or maintain immunological tolerance to innocuous dietary antigens, IgE production, and the release of histamine and other mediators upon exposure to a food allergen. Of the different FAs, peanut allergy has the highest incidence of severe allergic responses, including systemic anaphylaxis. Despite the recent FDA approval of peanut oral immunotherapy and other investigational immunotherapies, a loss of protection following cessation of therapy can occur, suggesting that these therapies do not address the underlying immune response driving FA. Our lab has shown that liver-directed gene therapy with an adeno-associated virus (AAV) vector induces transgene product-specific regulatory T cells (Tregs), eradicates pre-existing pathogenic antibodies, and protects against anaphylaxis in several models, including ovalbumin induced FA. In an epicutaneous peanut allergy mouse model, the hepatic AAV co-expression of four peanut antigens Ara h1, Ara h2, Ara h3, and Ara h6 together or the single expression of Ara h3 prevented the development of a peanut allergy. Since FA patients show a reduction in Treg numbers and/or function, we believe our approach may address this unmet need.

Commensal microbiome and gastrointestinal mucosal immunity: Harmony and conflict with our closest neighbor.

The gastrointestinal tract contains a wide range of microorganisms that have evolved alongside the immune system of the host. The intestinal mucosa maintains balance within the intestines by utilizing the mucosal immune system, which is controlled by the complex gut mucosal immune network. This review aims to comprehensively introduce current knowledge of the gut mucosal immune system, focusing on its interaction with commensal bacteria. The gut mucosal immune network includes gut-associated lymphoid tissue, mucosal immune cells, cytokines, and chemokines. The connection between microbiota and the immune system occurs through the engagement of bacterial components with pattern recognition receptors found in the intestinal epithelium and antigen-presenting cells. This interaction leads to the activation of both innate and adaptive immune responses. The interaction between the microbial community and the host is vital for maintaining the balance and health of the host's mucosal system. The gut mucosal immune network maintains a delicate equilibrium between active immunity, which defends against infections and damaging non-self antigens, and immunological tolerance, which allows for the presence of commensal microbiota and dietary antigens. This balance is crucial for the maintenance of intestinal health and homeostasis. Disturbance of gut homeostasis leads to enduring or severe gastrointestinal ailments, such as colorectal cancer and inflammatory bowel disease. Utilizing these factors can aid in the development of cutting-edge mucosal vaccines that have the ability to elicit strong protective immune responses at the primary sites of pathogen invasion.

Discovery and characterization of dietary antigens in oral tolerance.

Food antigens elicit immune tolerance through the action of regulatory T cells (Tregs) in the intestine. Although antigens that trigger common food allergies are known, the epitopes that mediate tolerance to most foods have not been described. Here, we identified murine T cell receptors specific for maize, wheat, and soy, and used expression cloning to de-orphan their cognate epitopes. All of the epitopes derive from seed storage proteins that are resistant to degradation and abundant in the edible portion of the plant. Multiple unrelated T cell clones were specific for an epitope at the C-terminus of 19 kDa alpha-zein, a protein from maize kernel. An MHC tetramer loaded with this antigen revealed that zein-specific T cells are predominantly Tregs localized to the intestine. These cells, which develop concurrently with weaning, constitute up to 2% of the peripheral Treg pool. Bulk and single-cell RNA sequencing revealed that these cells express higher levels of immunosuppressive markers and chemokines compared to other Tregs. These data suggest that immune tolerance to plant-derived foods is focused on a specific class of antigens with common features, and they reveal the functional properties of naturally occurring food-specific Tregs.

Astragalus polysaccharide: implication for intestinal barrier, anti-inflammation, and animal production.

Intestine is responsible for nutrients absorption and plays a key role in defending against various dietary allergens, antigens, toxins, and pathogens. Accumulating evidence reported a critical role of intestine in maintaining animal and human health. Since the use of antibiotics as growth promoters in animal feed has been restricted in many countries, alternatives to antibiotics have been globally investigated, and polysaccharides are considered as environmentally friendly and promising alternatives to improve intestinal health, which has become a research hotspot due to its antibiotic substitution effect. Astragalus polysaccharide (APS), a biological macromolecule, is extracted from astragalus and has been reported to exhibit complex biological activities involved in intestinal barrier integrity maintenance, intestinal microbiota regulation, short-chain fatty acids (SCFAs) production, and immune response regulation, which are critical for intestine health. The biological activity of APS is related to its chemical structure. In this review, we outlined the source and structure of APS, highlighted recent findings on the regulation of APS on physical barrier, biochemical barrier, immunological barrier, and immune response as well as the latest progress of APS as an antibiotic substitute in animal production. We hope this review could provide scientific basis and new insights for the application of APS in nutrition, clinical medicine and health by understanding particular effects of APS on intestine health, anti-inflammation, and animal production.

Early life imprinting of intestinal immune tolerance and tissue homeostasis.

Besides its canonical role in protecting the host from pathogens, the immune system plays an arguably equally important role in maintaining tissue homeostasis. Within barrier tissues that interface with the external microenvironment, induction of immune tolerance to innocuous antigens, such as commensal, dietary, and environmental antigens, is key to establishing immune homeostasis. The early postnatal period represents a critical window of opportunity in which parallel development of the tissue, immune cells, and microbiota allows for reciprocal regulation that shapes the long-term immunological tone of the tissue and subsequent risk of immune-mediated diseases. During early infancy, the immune system appears to sacrifice pro-inflammatory functions, prioritizing the establishment of tissue tolerance. In this review, we discuss mechanisms underlying early life windows for intestinal tolerance with a focus on newly identified RORγt+ antigen-presenting cells-Thetis cells-and highlight the role of the intestinal microenvironment in shaping intestinal immune system development and tolerance.

Gut bacteria-derived serotonin promotes immune tolerance in early life.

The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remain largely undefined. Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin, and that specific gut bacteria directly produce serotonin while down-regulating monoamine oxidase A to limit serotonin breakdown. We found that serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye and inhibit mTOR activation, thereby promoting the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine. Oral gavage of serotonin into neonatal mice resulted in long-term T cell-mediated antigen-specific immune tolerance toward both dietary antigens and commensal bacteria. Together, our study has uncovered an important role for specific gut bacteria to increase serotonin availability in the neonatal gut and identified a function of gut serotonin in shaping T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.

Group 3 innate lymphoid cells in intestinal health and disease.

The gastrointestinal tract is an immunologically rich organ, containing complex cell networks and dense lymphoid structures that safeguard this large absorptive barrier from pathogens, contribute to tissue physiology and support mucosal healing. Simultaneously, the immune system must remain tolerant to innocuous dietary antigens and trillions of normally beneficial microorganisms colonizing the intestine. Indeed, a dysfunctional immune response in the intestine underlies the pathogenesis of numerous local and systemic diseases, including inflammatory bowel disease, food allergy, chronic enteric infections or cancers. Here, we discuss group 3 innate lymphoid cells (ILC3s), which have emerged as orchestrators of tissue physiology, immunity, inflammation, tolerance and malignancy in the gastrointestinal tract. ILC3s are abundant in the developing and healthy intestine but their numbers or function are altered during chronic disease and cancer. The latest studies provide new insights into the mechanisms by which ILC3s fundamentally shape intestinal homeostasis or disease pathophysiology, and often this functional dichotomy depends on context and complex interactions with other cell types or microorganisms. Finally, we consider how this knowledge could be harnessed to improve current treatments or provoke new opportunities for therapeutic intervention to promote gut health.

A218 TRADING ONE PROBLEM FOR ANOTHER? THE EMERGENCE OF LYMPHOCYTIC ESOPHAGITIS IN A PEDIATRIC PATIENT WITH EOSINOPHILIC ESOPHAGITIS AFTER TREATMENT WITH DUPILUMAB

Abstract Background Eosinophilic esophagitis (EoE) is a Th2 driven chronic, inflammatory disorder defined by esophageal dysfunction and a peak eosinophil count (PEC) ≧ 15 eosinophils/high-power field on biopsy. Dupilumab, a human monoclonal antibody that inhibits IL-4 and IL-13 signaling was recently approved for use in Canada in children with EoE. There is limited data on the histologic abnormalities found with reintroduction of dietary triggers on dupilumab. Aims To describe emergence of lymphocytic esophagitis without eosinophilia observed during food reintroduction in a pediatric patient with EoE on dupilumab. Methods Case report and literature review. Results We present a 14-year-old boy with extensive food allergies, eczema, asthma and treatment refractory EoE. After failing to improve with proton-pump inhibitor (PPI), food elimination diet and topical steroids, he was started on an elemental formula with concomitant PPI. This resulted in symptomatic and histologic remission, however food restriction led to poor quality of life. The patient was started on dupilumab 200 mg every 2 weeks and had a dramatic improvement in his disease course. Over 2 years on treatment, several allergic foods were reintroduced with normal histologic biopsies. However, two dietary challenges led to the emergence of lymphocytic esophagitis with basal zone hyperplasia (BZH) and dilated intercellular spaces (DIS), but no eosinophilia. Subsequent removal of the dietary antigen and endoscopic reassessment led to normal biopsies, without lymphocytic or eosinophilic infiltration. Lymphocytic esophagitis is rare in children and the etiology is unknown; it is characterized by increased intraepithelial lymphocytes without eosinophils or neutrophils, and associated spongiosis. The emergence of lymphocytic esophagitis was unexpected and subsequent normalization of histology with removal of an antigen suggests that the lymphocytic pattern observed was driven by the allergic food. This may indicate that IL-4/IL-13 antagonism by dupilumab affects other immune signaling pathways, resulting in a lymphocytic-predominant inflammatory response upon exposure to allergic food antigens. Conclusions Dupilumab is a promising new medication in the management of pediatric EoE, particularly in the extremely atopic patient. In our case, the use of dupilumab led to improved antigen tolerance and quality of life. However, the emergence of lymphocytic esophagitis was unexpected, and the natural history and prognosis of this condition is not well defined. This is the first case to describe the emergence of lymphocytic esophagitis in a patient treated for eosinophilic esophagitis with dupilumab, and its subsequent resolution with dietary exclusion. Funding Agencies None

Extraction of the CDRH3 sequence of the mouse antibody repertoire selected upon influenza virus infection by subtraction of the background antibody repertoire.

As specific interactions between antigens and cell-surface antibodies trigger the proliferation of B-cell clones, the frequency of each antibody sequence in the samples reflects the size of each clonal population. Nevertheless, it is extremely difficult to extract antigen-specific antibody sequences from the comprehensive bulk antibody sequences obtained from blood samples due to repertoire bias influenced by exposure to dietary antigens and other infectious agents. This issue can be addressed by subtracting the background noise from the post-immunization or post-infection repertoire data. In the present study, we propose a method to quantify repertoire data from comprehensive repertoire data. This method allowed subtraction of the background repertoire, resulting in more accurate extraction of expanded antibody repertoires upon influenza virus infection. This accurate extraction of antigen- or infection-specific repertoire information is a useful tool for vaccine evaluation.

Probiotics in Infancy and Childhood for Food Allergy Prevention and Treatment.

Food allergy represents a failure of oral tolerance mechanisms to dietary antigens. Over the past few years, food allergies have become a growing public health problem worldwide. Gut microbiota is believed to have a significant impact on oral tolerance to food antigens and in initiation and maintenance of food allergies. Therefore, probiotics have also been proposed in this field as a possible strategy for modulating both the gut microbiota and the immune system. In recent years, results from preclinical and clinical studies suggest a promising role for probiotics in food allergy prevention and treatment. However, future studies are needed to better understand the mechanisms of action of probiotics in food allergies and to design comparable study protocols using specific probiotic strains, defined doses and exposure times, and longer follow-up periods.

Intestinal factors promoting the development of RORγt+ cells and oral tolerance.

The gastrointestinal tract has to harmonize the two seemingly opposite functions of fulfilling nutritional needs and avoiding the entry of pathogens, toxins and agents that can cause physical damage. This balance requires a constant adjustment of absorptive and defending functions by sensing environmental changes or noxious substances and initiating adaptive or protective mechanisms against them through a complex network of receptors integrated with the central nervous system that communicate with cells of the innate and adaptive immune system. Effective homeostatic processes at barrier sites take the responsibility for oral tolerance, which protects from adverse reactions to food that cause allergic diseases. During a very specific time interval in early life, the establishment of a stable microbiota in the large intestine is sufficient to prevent pathological events in adulthood towards a much larger bacterial community and provide tolerance towards diverse food antigens encountered later in life. The beneficial effects of the microbiome are mainly exerted by innate and adaptive cells that express the transcription factor RORγt, in whose generation, mediated by different bacterial metabolites, retinoic acid signalling plays a predominant role. In addition, recent investigations indicate that food antigens also contribute, analogously to microbial-derived signals, to educating innate immune cells and instructing the development and function of RORγt+ cells in the small intestine, complementing and expanding the tolerogenic effect of the microbiome in the colon. This review addresses the mechanisms through which microbiota-produced metabolites and dietary antigens maintain intestinal homeostasis, highlighting the complementarity and redundancy between their functions.

Mechanistic Insights into Eosinophilic Esophagitis: Therapies Targeting Pathophysiological Mechanisms.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by eosinophilic infiltration of the esophagus. It arises from a complex interplay of genetic predisposition (susceptibility loci), environmental triggers (allergens and dietary antigens), and a dysregulated immune response, mainly mediated by type 2 T helper cell (Th2)-released cytokines, such as interleukin (IL)-4, IL-5, and IL-13. These cytokines control eosinophil recruitment and activation as well as tissue remodeling, contributing to the characteristic features of EoE. The pathogenesis of EoE includes epithelial barrier dysfunction, mast cell activation, eosinophil degranulation, and fibrosis. Epithelial barrier dysfunction allows allergen penetration and promotes immune cell infiltration, thereby perpetuating the inflammatory response. Mast cells release proinflammatory mediators and promote eosinophil recruitment and the release of cytotoxic proteins and cytokines, causing tissue damage and remodeling. Prolonged inflammation can lead to fibrosis, resulting in long-term complications such as strictures and dysmotility. Current treatment options for EoE are limited and mainly focus on dietary changes, proton-pump inhibitors, and topical corticosteroids. Novel therapies targeting key inflammatory pathways, such as monoclonal antibodies against IL-4, IL-5, and IL-13, are emerging in clinical trials. A deeper understanding of the complex pathogenetic mechanisms behind EoE will contribute to the development of more effective and personalized therapeutic strategies.

Tolerance to Dietary Antigens in the Upper Intestine Through Chopping of Gasdermin D

Tolerance to Dietary Antigens in the Upper Intestine Through Chopping of Gasdermin D