@article{Fu:2026:10.1111/all.70244,
author = {Fu, H and Sun, P and Yuan, X and Yao, L and Hua, Q and Li, Y and Xuan, S and Zeng, X and Adcock, IM and Yao, X and Jia, M},
doi = {10.1111/all.70244},
journal = {Allergy},
title = {Epithelial-Associated CD207+ DCs Link Allergen Sensing and IL-25-Driven Th2 Inflammation in Asthma.},
url = {http://dx.doi.org/10.1111/all.70244},
year = {2026}
}

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TY  - JOUR
AB  - BACKGROUND: IL-25 is a key epithelial-derived alarmin associated with T2-high asthma, yet its downstream mechanisms remain poorly defined. CD207 (Langerin)+ dendritic cells (DCs) are localized at the airway epithelial interface. However, whether these cells respond to epithelial-derived cytokines and contribute to the Th2 immune response in asthma remains unclear. METHODS: Single-cell RNA-seq from healthy human lungs was analyzed to define the transcriptomic features of CD207+ DCs. Their function was validated in a house dust mite (HDM)-induced asthma model using Cd207-/- mice. Flow cytometry was performed on lung and mediastinal lymph nodes. DC-T cell co-cultures were used to assess Th2 polarization. Epithelial-DC interactions were evaluated using transwell co-culture with ALI-differentiated tracheal epithelial cells. Clinical relevance was examined in airway samples from asthma patients in the U-BIOPRED cohort. RESULTS: CD207+ DCs were enriched in intraepithelial compartments and exhibited increased MHC-II and Claudin-1 expression. In asthma, their abundance correlated with T2 signatures and Th2 markers (CRTH2, ST2). CD207 deletion reduced HDM uptake, Th2 cytokines, airway inflammation, and Th2 differentiation. IL-25 induced CD207+ DCs and enhanced their Th2-polarizing capacity in vitro. An IL-25-CD207 co-expression score correlated with IL-4/IL-5/IL-13 levels and was higher in steroid-naïve patients with severe asthma. CONCLUSION: Our study identifies CD207+ DCs as epithelial-associated antigen-presenting cells that bridge IL-25 signaling and Th2 polarization in allergic asthma. Targeting the IL-25-CD207 axis may offer therapeutic opportunities for T2-high asthma.
AU  - Fu,H
AU  - Sun,P
AU  - Yuan,X
AU  - Yao,L
AU  - Hua,Q
AU  - Li,Y
AU  - Xuan,S
AU  - Zeng,X
AU  - Adcock,IM
AU  - Yao,X
AU  - Jia,M
DO  - 10.1111/all.70244
PY  - 2026///
TI  - Epithelial-Associated CD207+ DCs Link Allergen Sensing and IL-25-Driven Th2 Inflammation in Asthma.
T2  - Allergy
UR  - http://dx.doi.org/10.1111/all.70244
UR  - https://www.ncbi.nlm.nih.gov/pubmed/41623094
ER  - 

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