Environmental determinants of immune tolerance in asthma and allergy.

Prevalence of allergic diseases has increased globally, reflecting environmental and behavioral changes. The exposome concept encompasses cumulative chemical, microbial, nutritional, psychosocial, and physical exposures across the life course, offering a unifying framework to understand how immune tolerance is shaped or disrupted. Emerging evidence highlights that early-life exposures are particularly critical. Pollutants, endocrine disruptors, microbial deprivation, dietary shifts, and psychosocial stress contribute to barrier dysfunction, dysbiosis, and immune dysregulation, favoring Th2 dominance and allergy development. In contrast, exposures that enhance biodiversity, microbial diversity, pollution-free air, and balanced nutrition support active tolerance development, especially via regulatory T cells. Mechanistic insights point to the barrier-microbiota-immune axis as central pathways linking the environment to allergic outcomes. Translational studies, including biodiversity enrichment interventions, maternal and infant dietary strategies, and microbiome-based therapies, illustrate the potential of exposome-informed approaches to allergy prevention. However, major challenges remain in measuring complex exposure mixtures, identifying causal pathways, and integrating exposome data with systems immunology. This review synthesizes current knowledge on how the exposome modulates immune tolerance and outlines future research directions toward precision prevention. A deeper understanding of these interactions is essential to address the rising global allergy burden.

• Publication year

  2025

• Venue

  Immunology Letters

• Publication date

  2025-10-01

• Fields of study

  Medicine, Environmental Science

• Identifiers
  DOI 10.1016/j.imlet.2025.107102PMID 41076098
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The odds of developing asthma and wheeze among children and adolescents exposed to particulate matter: a systematic review and meta-analysis

  2025cited by this paper
• Early Life Allergen Exposure and Its Influence on Risk of Atopic Disease.

  2025cited by this paper
• Cumulative pregnancy and postnatal environmental exposures impact social behaviour in male mice associated with epigenetic, ribosomal, and immune dysregulation

  2025cited by this paper
• The intestinal barrier: a pivotal role in health, inflammation, and cancer.

  2025cited by this paper
• Polyphenol Intake During Pregnancy and Childhood Asthma and Atopic Disorders: A Systematic Review

  2025cited by this paper
• Systemic barrier dysfunction in type 2 inflammation diseases: perspective in the skin, airways, and gastrointestinal tract

  2025cited by this paper
• Air Pollution and Childhood Asthma Hospitalizations in Chengdu, China: A Time-Series Study

  2025cited by this paper
• Association between exposure to airborne endocrine disrupting chemicals and asthma in children or adolescents: A systematic review and meta-analysis.

  2025cited by this paper
• The role of the early-life gut microbiome in childhood asthma

  2025cited by this paper
• The gut microbiome and cross-reactivity of food allergens: current understanding, insights, and future directions

  2025cited by this paper
• Immune Tolerance Regulation Is Critical to Immune Homeostasis

  2025cited by this paper
• Systems immunology: When systems biology meets immunology

  2025cited by this paper
• Intradermally Administered Retinoic Acid or Vitamin D3-Loaded Liposomes Induce Tolerogenic Skin Dendritic Cells

  2025cited by this paper
• Folic acid supplementation during pregnancy alleviates food allergy in offspring by inhibiting mast cell degranulation.

  2025cited by this paper
• The epithelial barrier theory proposes a comprehensive explanation for the origins of allergic and other chronic noncommunicable diseases

  2025cited by this paper
• Maternal dietary inflammatory index during pregnancy and the risk of offspring allergic disease

  2025cited by this paper
• Diet Diversity and Adherence to a Mediterranean Diet Pattern in Pregnancy Is Protective Against the Development of Early-Childhood Atopic Dermatitis

  2025cited by this paper
• Epigenetics, human imprintome, and chronic diseases

  2025cited by this paper
• Phthalates and bisphenols early-life exposure, and childhood allergic conditions: a pooled analysis of cohort studies

  2025cited by this paper
• Advancing Exposomics: From Concept to Practice in Environmental Health Sciences.

  2025cited by this paper
• Inhalant Mediated Allergy: Immunobiology, Clinical Manifestations and Diagnosis

  2025cited by this paper
• PM2.5 exacerbates nasal epithelial barrier dysfunction in allergic rhinitis by inducing NLRP3-mediated pyroptosis via the AhR/CYP1A1/ROS axis.

  2025cited by this paper
• Skin damage signals mediate allergic sensitization to spatially unlinked antigen.

  2025cited by this paper
• Dietary Polyphenols, Plant Metabolites, and Allergic Disorders: A Comprehensive Review

  2024cited by this paper
• Skin‐centered strategies in food allergy prevention

  2024cited by this paper
• Environmental chemical-wide associations with immune biomarkers in US adults: A cross-sectional analysis

  2024cited by this paper
• Food Allergy Risk: A Comprehensive Review of Maternal Interventions for Food Allergy Prevention

  2024cited by this paper
• Global, regional and national epidemiology of allergic disorders in children from 1990 to 2019: findings from the Global Burden of Disease study 2019

  2024cited by this paper
• Short-chain fatty acids: linking diet, the microbiome and immunity

  2024cited by this paper
• Probiotics supplementation during pregnancy or infancy on multiple food allergies and gut microbiota: a systematic review and meta-analysis

  2024cited by this paper
• Gut bacteria–derived serotonin promotes immune tolerance in early life

  2024cited by this paper
• Questionnaire-based exposome-wide association studies for common diseases in the Personalized Environment and Genes Study.

  2024cited by this paper
• Core fucosylation of maternal milk N-glycans imparts early-life immune tolerance through gut microbiota-dependent regulation in RORγt+ Treg cells.

  2024cited by this paper
• The Immunobiology and Treatment of Food Allergy.

  2024cited by this paper
• Probiotics in Infancy and Childhood for Food Allergy Prevention and Treatment

  2024cited by this paper
• Atmospheric environment and persistence of pediatric asthma: A population-based cohort study.

  2024cited by this paper
• Recent advances in the epithelial barrier theory

  2024cited by this paper
• The Effect of Climate Change on Allergen and Irritant Exposure.

  2024cited by this paper
• Identification of antigen-presenting cell-T cell interactions driving immune responses to food

  2024cited by this paper
• How the early life microbiome shapes immune programming in childhood asthma and allergies.

  2024cited by this paper
• Systematic review on maternal dietary patterns during pregnancy and offspring allergy

  2024cited by this paper
• A genome-wide meta-analysis reveals shared and population-specific variants for allergic sensitization.

  2024cited by this paper
• Is gastrointestinal epithelial barrier dysfunction the only responsible for sensitization to food allergens?

  2024cited by this paper
• A spatial human thymus cell atlas mapped to a continuous tissue axis

  2024cited by this paper
• Global change, climate change, and asthma in children: Direct and indirect effects - A WAO Pediatric Asthma Committee Report

  2024cited by this paper
• Association between maternal perinatal stress and depression and infant DNA methylation in the first year of life

  2024cited by this paper
• Environmental exposures influence multigenerational epigenetic transmission

  2024cited by this paper
• Probiotics and other adjuvants in allergen-specific immunotherapy for food allergy: a comprehensive review

  2024cited by this paper
• Maternal exercise during pregnancy is associated with reduced risk of asthma in the child: A prospective birth cohort study.

  2024cited by this paper
• The epithelial barrier theory and its associated diseases

  2024cited by this paper
• Regulatory T cells and their role in allergic disease

  2024cited by this paper
• Gut microbiota wellbeing index predicts overall health in a cohort of 1000 infants

  2024cited by this paper
• Reconceptualizing and Defining Exposomics within Environmental Health: Expanding the Scope of Health Research

  2024cited by this paper
• Hit me baby one more time…with microbial IPA.

  2024cited by this paper
• Effect of different delivery modes on intestinal microbiota and immune function of neonates

  2024cited by this paper
• Antibiotic-driven dysbiosis in early life disrupts indole-3-propionic acid production and exacerbates allergic airway inflammation in adulthood.

  2024cited by this paper
• Gut microbiota-derived metabolites tune host homeostasis fate

  2024cited by this paper
• Gestational exposure to environmental chemicals and epigenetic alterations in the placenta and cord blood mononuclear cells

  2024cited by this paper
• The Legacy of Redlining: Increasing Childhood Asthma Disparities Through Neighborhood Poverty.

  2024cited by this paper
• Climate Change, Exposome Change, and Allergy: A Review.

  2023cited by this paper
• Environmental Exposures may Hold the Key; Impact of Air Pollution, Greenness, and Rural/Farm Lifestyle on Allergic Outcomes

  2023cited by this paper
• EVALUATION OF SELECTED ASPECTS OF THE HYGIENE HYPOTHESIS AND THEIR EFFECT ON THE INCIDENCE OF ALLERGY

  2023cited by this paper
• Epigenetics and Social Inequalities in Asthma and Allergy.

  2023cited by this paper
• Prevention of food allergy in infancy: the role of maternal interventions and exposures during pregnancy and lactation.

  2023cited by this paper
• Organophosphate-Pesticide-Mediated Immune Response Modulation in Invertebrates and Vertebrates

  2023cited by this paper
• Long-term tolerance to skin commensals is established neonatally through a specialized dendritic cell subgroup.

  2023cited by this paper
• 2022 Fleming Prize Lecture: diet-microbe-host interaction in early life.

  2023cited by this paper
• Regulation of short-chain fatty acids in the immune system

  2023cited by this paper
• Geographical Differences of Risk of Asthma and Allergic Rhinitis according to Urban/Rural Area: a Systematic Review and Meta-analysis of Cohort Studies

  2023cited by this paper
• From Amish farm dust to bacterial lysates: The long and winding road to protection from allergic disease.

  2023cited by this paper
• The Effect of Breastfeeding on Food Allergies in Newborns and Infants

  2023cited by this paper
• When the allergy alarm bells toll: The role of Toll-like receptors in allergic diseases and treatment

  2023cited by this paper
• Diet-microbe-host interaction in early life

  2023cited by this paper
• Skin and oral intervention for food allergy prevention based on dual allergen exposure hypothesis

  2023cited by this paper
• The methylation profile of IL4, IL5, IL10, IFNG and FOXP3 associated with environmental exposures differed between Polish infants with the food allergy and/or atopic dermatitis and without the disease

  2023cited by this paper
• Early introduction is not enough: CSACI statement on the importance of ongoing regular ingestion as a means of food allergy prevention

  2023cited by this paper
• Environmental exposures in early-life and general health in childhood

  2023cited by this paper
• Longitudinal analysis of the impact of smoking exposure on atopic indices and allergies in early childhood

  2023cited by this paper
• Biomarkers of organophosphate insecticides exposure and asthma in general US adults: findings from NHANES 1999–2018 data

  2023cited by this paper
• Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review

  2023cited by this paper
• Commensal Collaborations: Food Allergy and the Microbiome.

  2023cited by this paper
• The immunological and structural epidermal barrier dysfunction and skin microbiome in atopic dermatitis-an update

  2023cited by this paper
• Prenatal vitamin D deficiency exposure leads to long-term changes in immune cell proportions

  2023cited by this paper
• New insight into the role of fibroblasts in the epithelial immune microenvironment in the single-cell era

  2023cited by this paper
• Probiotics and the Potential of Genetic Modification as a Possible Treatment for Food Allergy

  2023cited by this paper
• Effects of Early Diet on the Prevalence of Allergic Disease in Children: A Systematic Review and Meta-Analysis

  2023cited by this paper
• Fungi and bacteria in the beds of rural and urban infants correlate with later risk of atopic diseases

  2023cited by this paper
• Tolerogenic dendritic cells and TLR4/IRAK4/NF-κB signaling pathway in allergic rhinitis

  2023cited by this paper
• Immune Activation Profiles Elicited by Distinct, Repeated TLR Agonist Infusions in Rhesus Macaques.

  2023cited by this paper
• A missing jigsaw within the hygiene hypothesis: Low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection

  2023cited by this paper
• Introduction of allergenic food to infants and allergic and autoimmune conditions: a systematic review and meta-analysis

  2023cited by this paper
• Epithelial barrier hypothesis: Effect of the external exposome on the microbiome and epithelial barriers in allergic disease

  2022cited by this paper
• Prebiotic Supplementation During Gestation Induces a Tolerogenic Environment and a Protective Microbiota in Offspring Mitigating Food Allergy

  2022cited by this paper
• Loss of PP4 contributes to diesel exhaust particles‐induced epithelial barrier integrity disruption and alarmins release

  2022cited by this paper
• The hygiene hypothesis for allergy – conception and evolution

  2022cited by this paper
• Intestinal epithelium in early life

  2022cited by this paper
• Prenatal exposure to ambient air pollution associates with early life immune perturbations.

  2022cited by this paper
• ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut

  2022cited by this paper
• Gut epithelial barrier damage caused by dishwasher detergents and rinse aids.

  2022cited by this paper
• A RORγt+ cell instructs gut microbiota-specific Treg cell differentiation

  2022cited by this paper

• No citing papers are available for this paper.