Barrier dysfunction in allergic diseases: Mechanisms, diagnosis, and therapeutic targeting
- 1The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, 250 Changgang East Rd, Haizhu, Guangzhou, 510260, China
- 2Corresponding author.
Abstract
Background: The rising prevalence of allergic diseases parallels increasing environmental factors that compromise epithelial barrier integrity. The “epithelial barrier hypothesis” has evolved, emphasizing that dysfunction of skin, gut, and airway epithelia can act as an early event contributing to allergic sensitization and comorbidity. Objective: This review synthesizes recent advances elucidating how barrier defects facilitate allergen passage, promote type 2 immunity, and contribute to the atopic march and atopic multimorbidity involving atopic dermatitis (AD), food allergy (FA), asthma, and allergic rhinitis (AR), which may follow multiple trajectories. Methods: We critically reviewed literature on barrier dysfunction in AD, FA, asthma, and AR, focusing on mechanisms, diagnostic biomarkers, and therapeutic interventions. Results: Distinct organ-specific mechanisms were identified: filaggrin deficiency and Staphylococcus aureus protease activity in AD; zonulin-associated tight junction opening and IL-13-driven epithelial changes in FA; virus-induced oxidative stress and air-pollution–mediated barrier impairment in asthma; and allergen protease–mediated tight junction disruption in AR. Sequential and overlapping barrier defects may contribute to the atopic march and allergic comorbidities. Barrier-related tools, including transepidermal water loss (TEWL), the lactulose/mannitol (L/M) ratio, nasal TEWL (nTEWL), and epithelial sampling-based assays, are increasingly used to assess epithelial integrity, although their clinical maturity differs across organs. Therapeutic strategies include emollients, microbiome-based interventions, allergen immunotherapy (AIT), and biologics, but direct barrier-restoring evidence remains variable. Conclusion: Integrating barrier assessment into clinical or translational evaluation and targeting barrier repair alongside anti-inflammatory therapy may provide new opportunities for modifying allergic disease trajectories and managing allergic comorbidities.
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BibTeX
@article{xiao2026barrier,
title = {{Barrier dysfunction in allergic diseases: Mechanisms, diagnosis, and therapeutic targeting}},
author = {Weichun Xiao and Shan Wang and Ailin Tao},
journal = {Allergy Medicine},
year = {2026},
month = oct,
doi = {10.1016/j.allmed.2026.100141},
url = {https://doi.org/10.1016/j.allmed.2026.100141},
note = {CC BY},
}
RIS
TY - JOUR
TI - Barrier dysfunction in allergic diseases: Mechanisms, diagnosis, and therapeutic targeting
AU - Weichun Xiao
AU - Shan Wang
AU - Ailin Tao
PY - 2026
DA - 2026/10/30
JO - Allergy Medicine
DO - 10.1016/j.allmed.2026.100141
UR - https://doi.org/10.1016/j.allmed.2026.100141
AB - Background: The rising prevalence of allergic diseases parallels increasing environmental factors that compromise epithelial barrier integrity. The “epithelial barrier hypothesis” has evolved, emphasizing that dysfunction of skin, gut, and airway epithelia can act as an early event contributing to allergic sensitization and comorbidity. Objective: This review synthesizes recent advances elucidating how barrier defects facilitate allergen passage, promote type 2 immunity, and contribute to the atopic march and atopic multimorbidity involving atopic dermatitis (AD), food allergy (FA), asthma, and allergic rhinitis (AR), which may follow multiple trajectories. Methods: We critically reviewed literature on barrier dysfunction in AD, FA, asthma, and AR, focusing on mechanisms, diagnostic biomarkers, and therapeutic interventions. Results: Distinct organ-specific mechanisms were identified: filaggrin deficiency and Staphylococcus aureus protease activity in AD; zonulin-associated tight junction opening and IL-13-driven epithelial changes in FA; virus-induced oxidative stress and air-pollution–mediated barrier impairment in asthma; and allergen protease–mediated tight junction disruption in AR. Sequential and overlapping barrier defects may contribute to the atopic march and allergic comorbidities. Barrier-related tools, including transepidermal water loss (TEWL), the lactulose/mannitol (L/M) ratio, nasal TEWL (nTEWL), and epithelial sampling-based assays, are increasingly used to assess epithelial integrity, although their clinical maturity differs across organs. Therapeutic strategies include emollients, microbiome-based interventions, allergen immunotherapy (AIT), and biologics, but direct barrier-restoring evidence remains variable. Conclusion: Integrating barrier assessment into clinical or translational evaluation and targeting barrier repair alongside anti-inflammatory therapy may provide new opportunities for modifying allergic disease trajectories and managing allergic comorbidities.
SN - 2949-9135
ER -