Allergic Phenotype Research Articles

243 TLR2/CD14 ligands from gram positive and gram negative bacteria inhibit IL-33 release from keratinocytes. Can diverse skin colonisation alone inhibit the allergic phenotype?

243 TLR2/CD14 ligands from gram positive and gram negative bacteria inhibit IL-33 release from keratinocytes. Can diverse skin colonisation alone inhibit the allergic phenotype?

Allergic Disease with Selective IgA Deficiency. Comment on Cinicola et al. The Allergic Phenotype of Children and Adolescents with Selective IgA Deficiency: A Longitudinal Monocentric Study. J. Clin. Med. 2022, 11, 5705.

I read the article titled 'The Allergic Phenotype of Children and Adolescents with Selective IgA Deficiency: A Longitudinal Monocentric Study' by Cinicola et al. with great interest [...].

Severity predictors of different phenotypes of T2 asthma endotype

BACKGROUND: Epidemiological studies have showed that severe asthma is observed in 5–10% of patients. It is considered as a major social and economic burden for the healthcare system.
 AIM: to perform a comparative analysis of clinical features of allergic and non-allergic phenotypes of T2 asthma and determine the most important predictors of severity.
 MATERIALS AND METHODS: We studied 150 patients with asthma (ages 18–65). Of these, 61 were diagnosed with T2 endotype of asthma. Clinical examination and allergy testing were performed. The potential predictors of severe asthma included: asthma phenotype, gender, age (including elderly age), daytime/nocturnal symptoms per week, asthma exacerbations that required systemic corticosteroid therapy and hospitalisations, the volume of forced exhalation in the first second (FEV1; % of predicted value), body mass index (kg/m2), concomitant diseases, smoking status, sensitization to non-infectious allergens and blood eosinophil count.
 RESULTS: Group 1 included 34 patients with allergic phenotype of asthma, group 2 ― 27 patients with non-allergic phenotype of T2 endotype of asthma. Univariate analyses revealed that subjects with non-allergic asthma were likely to have severe asthma (OR=3.14 [95% CI: 1.09–9.58]. Increased daytime symptoms per week, nocturnal symptoms per week, exacerbations that require systemic corticosteroids and hospitalisation were associated with asthma severity (OR=1.05 [95% CI: 1.01–1.11], 1.21 [95% CI: 1.05–1.45], 3.46 [95% CI: 1.68–10.19], 4 [95% CI: 1.75–12.32] and 4 [95% CI: 1.75–12.32], respectively), regardless of the disease phenotype. Lower FEV1 was associated with severe asthma (OR=0.96 [95% CI: 0.93–0.99]. Multivariate analysis showed that age, increased frequency of nocturnal symptoms, and lower FEV1 were associated with severe asthma.
 CONCLUSION: The certain clinical differences of allergic and non-allergic asthma could be revealed when analyzing anamnestic data and clinical findings. Increased frequency of nocturnal symptoms, decreased FEV1 and age are the most significant predictors of severe T2 endotype of asthma.

Fruit Pouch Consumption Does Not Associate with Early Manifestations of Allergic Disease.

Consumption of acidic fruit pouches in infancy may damage the epithelial barrier in the gastrointestinal tract and is suggested to increase allergy risk. We aimed to explore if a high fruit pouch consumption is associated with a higher incidence of early allergic manifestations. We included 2959 parent-child dyads from the Swedish prospective, population-based NorthPop birth cohort study with parentally reported data on frequency of fruit pouch consumption at 9 months of age, as well as parentally reported eczema, wheeze, physician-diagnosed asthma, and food allergy in the first 18 months of life. Immunoglobulin E levels (IgE) in serum (n = 1792), as response to a food mix and an inhalant mix, were determined at age 18 months. Compared with no consumption, daily consumption of one or more pouches at 9 months of age was associated with inhalant sensitization (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.06-4.87, n = 1792) but did not remain significant in the multivariable adjusted model (aOR 2.08, 95% CI 0.95-4.53, n = 1679). There were no associations between fruit pouch consumption and allergic manifestations at this young age. This study suggests that fruit pouch consumption is not associated with allergic phenotypes or IgE sensitization in early childhood.

Evaluation of serum levels of interferon beta and nucleotide binding and oligomerization domain 2 gene polymorphism in children with cough asthma phenotype: a case–control study

BackgroundIndividuals with asthma are thought to suffer from a variety of distinct disorders, or phenotypes, each of which is characterized by a unique combination of genetic and environmental factors. Syndromes that are exacerbated by allergens, non-allergic factors, and aspirin, as well as syndromes that are best differentiated by pathologic findings, response to therapy, and natural history, fall into this category. The best course of treatment for an individual patient with asthma can be determined by first determining his or her specific asthma phenotype and its underlying pathophysiology.Aim of the workExplore clinical characteristics, serum INF-β in cough asthma phenotype and allergic march asthmatic children. Also, to assess the association of NOD2 (rs2066845) gene polymorphism among those asthma phenotypes in Egyptian asthmatic children.Patients and methodsThe study included 64 cough phenotypic asthmatic children and 60 allergic march phenotypic asthmatic children in addition to 39 healthy controls (control group). The included children were subjected to full clinical history taking, full clinical examination, assessment of (total serum IgE, CBC for peripheral eosinophil percentage, cytokine profile (serum levels of INF-B), and genetic analysis: SNPs of NOD2 (rs2066845).ResultsThere was a significant increase in G allele frequency, in both homozygous (GG) and heterozygous (GC) states, among asthmatic children of cough and allergic march phenotypes compared to healthy controls, with no significant difference between the two phenotypes. In addition, serum INF-β was significantly lower in cough and allergic march phenotypic asthmatics with GG genotypes versus healthy controls of the same genotype.ConclusionsNOD2 (rs2066845) gene polymorphism is associated with both cough and allergic march asthma phenotypes in Egyptian asthmatic children. It was also shown that G allele may be implicated in asthma pathophysiology.

Effect of post-COVID syndrome on the quality of life of patients with allergic rhinitis and eosinophilic phenotype of chronic polyposis rhinosinusitis

BACKGROUND.An urgent issue of modern medicine is the study of the quality of life of people with post-COVID syndrome.Particular emphasis is placed on patients with various forms of allergic rhinitis associated with comorbid conditions such as polyposis rhinosinusitis.These diseases are still common and tend to increase.In this context, the study of the effect of conservative methods of treatment of allergic rhinitis and polyposis rhinosinus on the quality of life of patients will improve the effectiveness of the therapy.
 AIMS: To assess the impact of post-COVID syndrome on the quality of life of patients with various forms of allergic rhinitis and eosinophilic phenotype of chronic polyposis rhinosinusitis and to determine the effectiveness of conservative therapy.
 MATERIALS AND METHODS: In the period from May to December 2021, a study was conducted on the quality of life in the treatment of 62 patients against the background of post-covid syndrome, of which 32 patients suffered from polypous rhinosinusitis and 30 patients with allergic rhinitis.The disease of coronavirus infection was registered 2-3 months before the visit to the otorhinolaryngologist.The comparison groups included 65 people, including 33 patients with polypous rhinosinusitis and 32 with various forms of allergic rhinitis.The Russian version of the standard SF-36 questionnaire was used to collect anamnesis.A visual analogue scale was used to measure the intensity of rhinological symptoms.All patients were examined three times: before treatment, 1 and 3 months after the course of therapy.
 RESULTS: A comparative analysis of the quality of life indicators of patients with various forms of allergic rhinitis and polyposis rhinosinusitis showed a direct dependence on the condition of patients after a coronavirus infection.
 CONCLUSIONS: The use of the assessment of quality of life indicators at the stages of treatment of patients with various forms of allergic rhinitis and polypous rhinosinusitis against the background of post-covid syndrome makes it possible to determine the effectiveness of conservative therapy and timely adjust the treatment.

Dissecting Airborne Allergens.

Asthma is a heterogeneous and very complex group of diseases, and includes different clinical phenotypes depending on symptoms, progression, exacerbation patterns, or responses to treatment, among other characteristics. The allergic phenotype is the most frequent, especially in pediatric asthma. It is characterized by sensitization (the production of specific IgEs) to allergens and frequent comorbidity with rhinitis as well as atopic dermatitis. Given the complexity of allergic asthma, knowledge of it must be approached from different points of view: clinical, histological, physiological, epidemiological, biochemical, and immunological, among others. Since partial approaches do not allow for the understanding of this complexity, it is necessary to have multidimensional knowledge that helps in performing the optimal management of each case, avoiding a "blind men and elephant parable" approach. Allergens are antigens that trigger the production of specific IgE antibodies in susceptible individuals, who present symptoms that will depend on the type and intensity of the allergenic load as well as the tissue where the interaction occurs. Airborne allergens cause their effects in the respiratory tract and eyes, and can be indoor or outdoor, perennial, or seasonal. Although allergens such as mites, pollens, or animal dander are generally considered single particles, it is important to note that they contain different molecules which could trigger distinct specific IgE molecules in different patients. General practitioners, pediatricians, and other physicians typically diagnose and treat asthma based on clinical and pulmonary function data in their daily practice. This nonsystematic and nonexhaustive revision aims to update other topics, especially those focused on airborne allergens, helping the diagnostic and therapeutic processes of allergic asthma and rhinitis.

Response to Biologics and Clinical Remission in the Adult German Asthma Net Severe Asthma Registry Cohort.

Recently, criteria for evaluation of response to biologics have been proposed and the concept of clinical remission has gained attention as a possible goal even in severe asthma. To analyze the response and remission in the German Asthma Net severe asthma registry cohort. We included adults not using a biologic at baseline (V0) and compared patients treated between V0 and 1-year visit (V1) without using a biologic (group A) to patients starting with a biologic after V0 and continuing it up to V1 (group B). We applied the Biologics Asthma Response Score to quantify composite response in good, intermediate, or insufficient. We defined clinical remission (R) as absence of significant symptoms (Asthma Control Test score ≥ 20 at V1) in the absence of exacerbations and oral corticosteroid therapy. Group A included 233 and group B 210 patients, the latter receiving omalizumab (n= 33), mepolizumab (n= 40), benralizumab (n= 81), reslizumab (n= 1), or dupilumab (n= 56). At baseline, group B had less often an allergic phenotype (35.2% vs 41.6%), lower Asthma Control Test score (median, 12 vs 14), more exacerbations in the past year (median, 3 vs 2), and more often high-dose inhaled corticosteroid treatment (71.4% vs 51.5%) than group A. After 1 year of treatment, rates of response (good: 61.4% vs 34.8%; intermediate: 26.7% vs 42.9%; insufficient: 11.9% vs. 22.3%) and/or clinical remission (37.6% vs 17.2%) were higher in group B than in group A. Despite more severe asthma at baseline, patients treated with biologics had a markedly higher probability of achieving good clinical response and/or remission than patients treated without biologics.

Allergic Phenotypes and Sarcopenia: Evidence from Observational Studies and Mendelian Randomization Analysis.

The online version contains supplementary material available at 10.1007/s43657-023-00110-4.

Functional immunophenotyping of blood neutrophils identifies novel endotypes of viral response in preschool children with recurrent wheezing

Preschool children with recurrent wheezing are heterogeneous, with differing responses to respiratory viral infections. Although neutrophils are crucial for host defense, their function has not been studied in this population. We performed functional immunophenotyping on isolated blood neutrophils from 52 preschool children with recurrent wheezing (aeroallergen sensitization, n= 16; no sensitization, n= 36). Blood neutrophils were purified and cultured overnight with polyinosinic:polycytidylic acid [poly(I:C)] as a viral analog stimulus. Neutrophils underwent next-generation sequencing with Reactome pathway analysis and were analyzed for cytokine secretion, apoptosis, myeloperoxidase, and extracellular DNA release. CD14+ monocytes were also exposed to neutrophil culture supernatant and analyzed for markers of M1 and M2 activation. A total of 495 genes, related largely to the innate immune system and neutrophil degranulation, were differently expressed in children with versus without aeroallergen sensitization. Functional experiments identified more neutrophil degranulation and extracellular trap formation (ie, more myeloperoxidase and extracellular DNA) and less neutrophil proinflammatory cytokine secretion in children with aeroallergen sensitization. Neutrophils also shifted CD14+ monocytes to a more anti-inflammatory (ie, M2) phenotype in sensitized children and a more proinflammatory (ie, M1) phenotype in nonsensitized children. Although both groups experienced viral exacerbations, annualized exacerbation rates prompting unscheduled health care were also higher in children without aeroallergen sensitization after enrollment. Systemic neutrophil responses to viral infection differ by allergic phenotype and may be less effective in preschool children without allergic inflammation. Further studies of neutrophil function are needed in this population, which often has less favorable therapeutic responses to inhaled corticosteroids and other therapies directed at type 2-high inflammation.

Genetic Variants Leading to Urticaria and Angioedema and Associated Biomarkers.

Advances in next generation sequencing technologies, as well as their expanded accessibility and clinical use over the past 2 decades, have led to an exponential increase in the number of identified single gene disorders. Among these are primary atopic disorders-inborn errors of immunity resulting in severe allergic phenotypes as a primary presenting feature. Two cardinal aspects of type I immediate hypersensitivity allergic reactions are hives and angioedema. Mast cells (MCs) are frequent primary drivers of these symptoms, but other cells have also been implicated. Even where MC degranulation is believed to be the cause, mediator-induced symptoms may greatly vary among individuals. Angioedema-particularly in the absence of hives-may also be caused by hereditary angioedema conditions resulting from aberrant regulation of contact system activation and excessive bradykinin generation or impairment of vascular integrity. In these patients, swelling can affect unpredictable locations and fail to respond to MC-directed therapies. Genetic variants have helped delineate key pathways in the etiology of urticaria and nonatopic angioedema and led to the development of targeted therapies. Herein, we describe the currently known inherited and acquired genetic causes for these conditions, highlight specific features in their clinical presentations, and discuss the benefits and limitations of biomarkers that can help distinguish them.

Phenotypic features of respiratory function disorders in occupational asthma

The article is devoted to the study of spirographic indicators FEV1, FEV1/FVC, PEF, MEF75, MEF50, and MEF25 as the most informative indicators reflecting the state of bronchial patency at the level of the proximal and distal portions of the bronchial tree in various phenotypes of occupational asthma. The signs of respiratory distress are most pronounced in patients with the occupational COPD phenotype of occupational asthma. Significantly more favorable spirographic picture in terms of FVC, FEV1, PEF, and MEF25VC is observed in the allergic phenotype of occupational asthma. Dynamic determination of forced expiratory flow in various phenotypes of occupational bronchial asthma allows to improve the diagnosis of obstructive disorders in this pathology, optimize the choice of therapeutic and preventive tactics, and predict the course of this pathology.

Molecular Mapping of Allergen Exposome among Different Atopic Phenotypes.

Climate change and exposure to environmental pollutants play a key role in the onset and aggravation of allergic diseases. As different climate-dependent patterns of molecular immunoglobulin E (IgE) reactivity have been regionally described, we sought to investigate the evolving allergen exposome in distinctive allergic phenotypes and subtropical weather conditions through a Precision Allergy Molecular Diagnosis (PAMD@) model. Concurrent sensitization to several house dust mites (HDM) and storage mite molecules were broadly dominant in the investigated cohort, followed by the major cat allergen Fel d 1, and regardless of the basal allergic disease. Although a complex repertoire of allergens was recognized, a steadily increasing number of IgE binding molecules was associated with the complexity of the underlying atopic disease. Besides the highly prevalent IgE responses to major HDM allergens, Der p 21, Der p 5, and Der p 7 also showed up as serodominant molecules, especially in subjects bothered by asthma and atopic dermatitis. The accurate characterization of the external exposome at the molecular level and their putative role as clinically relevant allergens is essential to elucidate the phenotypic diversity of atopic disease in terms of personalized diagnosis and therapy.

Deletion of Miro1 in airway club cells potentiates allergic asthma phenotypes.

Mitochondria are multifaceted organelles necessary for numerous cellular signaling and regulatory processes. Mitochondria are dynamic organelles, trafficked and anchored to subcellular sites depending upon the cellular and tissue requirements. Precise localization of mitochondria to apical and basolateral membranes in lung epithelial cells is important for key mitochondrial processes. Miro1 is an outer mitochondrial membrane GTPase that associates with adapter proteins and microtubule motors to promote intracellular movement of mitochondria. We show that deletion of Miro1 in lung epithelial cells leads to perinuclear clustering of mitochondria. However, the role of Miro1 in epithelial cell response to allergic insults remains unknown. We generated a conditional mouse model to delete Miro1 in Club Cell Secretory Protein (CCSP) positive lung epithelial cells to examine the potential roles of Miro1 and mitochondrial trafficking in the lung epithelial response to the allergen, house dust mite (HDM). Our data show that Miro1 suppresses epithelial induction and maintenance of the inflammatory response to allergen, as Miro1 deletion modestly induces increases in pro-inflammatory signaling, specifically IL-6, IL-33, CCL20 and eotaxin levels, tissue reorganization, and airway hyperresponsiveness. Furthermore, loss of Miro1 in CCSP+ lung epithelial cells blocks resolution of the asthmatic insult. This study further demonstrates the important contribution of mitochondrial dynamic processes to the airway epithelial allergen response and the pathophysiology of allergic asthma.

IL18 Gene Polymorphism Is Associated with Total IgE in Adult Subjects with Asthma.

The allergic asthma phenotype is characterized by a T helper type 2 (Th2) immune response, based on Immunoglobulin E (IgE)-mediated type 1 hypersensitivity reactions. Total IgE is the sum of all IgE types produced by the human body and is used as a biomarker of inflammation in asthma. We analysed data collected in 143 asthma cases (median age 42.1 years) from the general Italian population (GEIRD survey; 2008-2010) to identify single nucleotide polymorphisms (SNPs) in candidate genes that are associated with total IgE in adult subjects with asthma. These patients reported respiratory symptoms in response to perennial allergens and provided data on 166 SNPs tagging 50 candidate genes or gene regions. Replication of the statistically significant results was performed in 842 asthma cases from other European countries (ECRHS II survey; 1998-2002). SNP rs549908 in interleukin 18 (IL18) gene was significantly associated with total IgE in GEIRD, and this result was replicated in ECRHS II. SNP rs1063320 in the human leukocyte antigen G (HLA-G) gene was identified in GEIRD, but this association was not replicated in ECRHS II. Further investigating IL18 and its biological pathways could be important for developing new therapeutic targets, due to its involvement in inflammatory response processes.

Is Anisakis simplex a Trigger for Anaphylactic Reactions in Hereditary Alpha-Tryptasemia?

The prevalence of fish, seafood and Anisakis allergy varies greatly depending on country-specific eating habits, assuming that the highest consumption corresponds to the highest prevalence. Mediterranean countries are particularly affected. Hereditary Alpha-Tryptasemia (HaT) is a common autosomal dominant genetic trait recently identified. Although it is estimated to affect approximately 1 in 20 individuals of white European origin, a diagnostic method is not routinely available. Here by we present the cases of two families with different allergic reaction phenotypes to fish and seafood, IgE and no IgE mediated reactions. The current review focused on the impact of the diagnosis of HaT in families, particularly when the mutation is symptomatic and the affectation from an early age and in both sexes and finally this review tried to warn about the possible involvement of Anisakis in allergic reactions in patients with HaT.

Dupilumab improves long-term outcomes in patients with uncontrolled, moderate-to-severe GINA-based type 2 asthma, irrespective of allergic status.

Previous research has shown greater efficacy of dupilumab in patients with uncontrolled asthma and type 2 inflammation. We analyzed dupilumab's efficacy in patients from the TRAVERSE study with or without evidence of allergic asthma and type 2 inflammation per current GINA guidelines (≥150 eosinophils/μL or FeNO ≥20 ppb). All patients aged ≥12 years who rolled over from the placebo-controlled QUEST study (NCT02414854) to TRAVERSE (NCT02134028) received add-on dupilumab 300 mg every 2 weeks for up to 96 weeks. We assessed annualized severe asthma exacerbation rates (AERs) and changes from parent-study baseline (PSBL) in pre-bronchodilator FEV1 and 5-item asthma control questionnaire (ACQ-5) score in patients with moderate-to-severe type 2 asthma with and without evidence of allergic asthma at PSBL. In TRAVERSE, dupilumab consistently reduced AER across all subgroups. By Week 96, dupilumab increased pre-bronchodilator FEV1 from PSBL by 0.35-0.41 L in patients receiving placebo during QUEST (placebo/dupilumab) and 0.34-0.44 L in those receiving dupilumab during QUEST (dupilumab/dupilumab) with an allergic phenotype at baseline. In patients without evidence of allergic asthma, pre-bronchodilator FEV1 improved by 0.38-0.41 L and 0.33-0.37 L, respectively. By Week 48, ACQ-5 scores decreased from PSBL by 1.63-1.69 (placebo/dupilumab) and 1.74-1.81 (dupilumab/dupilumab) points across subgroups with allergic asthma, and 1.75-1.83 (placebo/dupilumab) and 1.78-1.86 (dupilumab/dupilumab) in those without. Long-term treatment with dupilumab reduced exacerbation rates and improved lung function and asthma control in patients with asthma with type 2 inflammation as per current GINA guidance and irrespective of evidence of allergic asthma.

Single-cell immune profiling of Meniere Disease patients

BackgroundMeniere Disease (MD) is an inner ear syndrome, characterized by episodes of vertigo, tinnitus and fluctuating sensorineural hearing loss. The pathological mechanism leading to sporadic MD is still poorly understood, however an allergic inflammatory response seems to be involved in some patients with MD. ObjectiveDecipher an immune signature associated with the syndrome. MethodsWe performed mass cytometry immune profiling on peripheral blood from MD patients and controls. We analyzed differences in state and differences in abundance of the different cellular subsets. IgE levels were quantified through ELISA on supernatant of cultured whole blood. ResultsWe have identified two clusters of individuals according to the single cell cytokine profile. These clusters presented differences in IgE levels, immune cell population abundance, including a reduction of CD56dim NK-cells, and changes in cytokine expression with a different response to bacterial and fungal antigens. ConclusionOur results support a systemic inflammatory response in some MD patients that show a type 2 response with allergic phenotype, which could benefit from personalized IL-4 blockers.

Prophylactic and therapeutic potential of magnolol-loaded PLGA-PEG nanoparticles in a chronic murine model of allergic asthma.

Magnolol is a chemically defined and active polyphenol extracted from magnolia plants possessing anti-allergic activity, but its low solubility and rapid metabolism dramatically hinder its clinical application. To improve the therapeutic effects, magnolol-encapsulated polymeric poly (DL-lactide-co-glycolide)-poly (ethylene glycol) (PLGA-PEG) nanoparticles were constructed and characterized. The prophylactic and therapeutic efficacy in a chronic murine model of OVA-induced asthma and the mechanisms were investigated. The results showed that administration of magnolol-loaded PLGA-PEG nanoparticles significantly reduced airway hyperresponsiveness, lung tissue eosinophil infiltration, and levels of IL-4, IL-13, TGF-β1, IL-17A, and allergen-specific IgE and IgG1 in OVA-exposed mice compared to their empty nanoparticles-treated mouse counterparts. Magnolol-loaded PLGA-PEG nanoparticles also significantly prevented mouse chronic allergic airway mucus overproduction and collagen deposition. Moreover, magnolol-encapsulated PLGA-PEG nanoparticles showed better therapeutic effects on suppressing allergen-induced airway hyperactivity, airway eosinophilic inflammation, airway collagen deposition, and airway mucus hypersecretion, as compared with magnolol-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles or magnolol alone. These data demonstrate the protective effect of magnolol-loaded PLGA-PEG nanoparticles against the development of allergic phenotypes, implicating its potential usefulness for the asthma treatment.

Premature Treg induction in early life results in FoxP3 instability post-weaning

Abstract Peripherally-derived RORγt+ regulatory T cells (Tregs) induced in early life are crucial for maintaining oral tolerance later in life, and the loss of these long-lived cells is associated with increased allergic and inflammatory phenotypes in several animal models. We have identified a predominant pathway of luminal antigen delivery that is associated with Treg development. Around weaning, microbial and dietary proteins are delivered to the colonic lamina propria via goblet cell-associated antigen passages (GAPs) and taken up by antigen presenting cells. GAP formation is inhibited by breastmilk-derived epidermal growth factor (EGF) which is highest in maternal milk at parturition and is diminished by weaning. We have previously shown that disruption of this process – via EGF receptor inhibition (EGFRi) day of life (DOL)4–8 or by conditional deletion of EGFR from goblet cells – results in premature antigen delivery. Consequently, this results in an early initial increase in FoxP3 expression in the colon that is unstable and, ultimately, lost by Tregs primed pre-weaning; this suggests that earlier education of T cells is incompatible with regulatory T cell differentiation in early life. EGFRi-treated FoxP3eGFP-Cre-ERT2ROSAlsl-YFPmice, whose FoxP3+ cells were YFP-labeled at DOL21, had a larger number of YFP+ T cells that lost FoxP3 expression than that of control mice, by DOL28. Further, compared to controls, wild-type mice treated with EGFRi DOL4–8 had increased IFNγ, TNFα, and IL-17a-expressing CD4 T cells when challenged with DSS colitis later in life. This suggests that early antigen delivery-associated FoxP3 instability may contribute to an increased propensity toward an inflammatory phenotype later in life.