Carina Beha

Background: Eosinophilic esophagitis (EoE) is a chronic immune‐mediated disease characterized by symptoms of esophageal dysfunction, such as dysphagia and food impaction, as well as eosinophilic inflammation and impaired epithelial barrier integrity, which promotes allergen influx. Environmental exposures that weaken the esophageal barrier, including surfactants found in personal care products such as sodium dodecyl sulfate (SDS) and cocamidopropyl betaine (CAPB), have been proposed as contributors to disease susceptibility. However, their direct effects on esophageal epithelial barrier function and associated molecular responses remain insufficiently characterized. Methods: We investigated the molecular and functional consequences of SDS and CAPB exposure in primary EoE‐derived esophageal organoids and air‐liquid interface cultures derived from biopsy tissue samples. We conducted transepithelial electrical resistance (TEER) measurements, paracellular flux assays, RNA sequencing, targeted and untargeted proteomics, and immunofluorescence imaging. Results: Treatment of esophageal organoids with SDS or CAPB (0–100 μg/mL) caused dose‐dependent cytotoxicity and barrier disruption, with SDS producing stronger effects. At 12.5 μg/mL, viability declined to ~30% with SDS versus ~60% with CAPB, accompanied by greater TEER reduction and ~2‐fold higher permeability. RNA‐seq of organoids exposed to 12.5 μg/mL for 24 h showed distinct transcriptomic clustering, with 2749 shared and > 1500 surfactant‐specific differentially expressed genes, indicating broad epithelial remodeling, cell‐cycle suppression, and stress responses, more pronounced under SDS. SDS preferentially activated inflammatory and innate immune pathways, which was supported by proteomic detection of elevated cytokines (TNF, IL‐8, IL‐18, etc.). Both surfactants induced keratinization, epidermal cell differentiation, and partial epithelial‐mesenchymal transition signatures, including increased vimentin without E‐cadherin loss. Conclusion: These findings demonstrate that common surfactants can induce coordinated epithelial stress responses in esophageal tissue models and may act as environmental aggravating factors in EoE at relatively low doses. This work underscores the need to consider mucosal exposure to consumer product ingredients in the context of epithelial barrier disorders, particularly surfactants such as SDS and CAPB, and supports efforts to refine formulations to minimize epithelial damage.

Background: Atopic dermatitis (AD) is a chronic type‐2 inflammatory skin disease characterized by eczema and epithelial barrier dysfunction. Along with the type‐2 cytokines IL‐4 and IL‐13, IL‐22 contributes to AD pathogenesis. To date, most skin studies rely on reconstructed keratinocytes, which do not represent the real skin response. Objective: Here, we report the distinct effects of IL‐4, IL‐13, and IL‐22 on bio‐stabilized human skin with intact barriers and immune cells. Methods: Spatial transcriptomics on AD ‐lesions and non‐lesional skin was performed. Ex vivo skin barrier integrity was evaluated using electrical impedance spectroscopy ( EIS ), RNA ‐sequencing, and untargeted proteomics, complemented by analyses of skin biopsies from dupilumab‐treated AD patients. Results: Spatial transcriptomics demonstrated that AD lesions showed reduced expression of key barrier genes, including CLDN1, FLG, and FLG2. IL‐4, IL‐13, and IL‐22 disrupted the skin barrier in the ex vivo human skin. Combining type‐2 cytokines and IL‐22 alone downregulated genes critical for barrier function and keratinization. In addition, IL‐4 and IL‐13 downregulated antimicrobial peptides, while IL‐22 upregulated them. Interestingly, IL‐4 and IL‐13 reduced IL‐22Rα1, and IL‐22 upregulated IL‐4Rα, suggesting immune cross‐regulation. Proteomic analysis confirmed that all three cytokines (IL‐4, IL‐13, and IL‐22) reduced the expression of key skin barrier proteins, particularly filaggrin and claudin‐1. Dupilumab treatment of AD patients for 3 months restored IL‐4/IL‐13‐dysregulated genes, whereas it had limited effect on IL22‐associated pathways. Conclusion: This comprehensive study provides insights into the distinct immune profiles following IL‐4, IL‐13, and IL‐22 stimulation on human skin, highlighting their complex interplay in disrupting skin barrier function and modulating innate immune responses.