Abstract
Asthma remains the most prevalent chronic respiratory condition affecting pediatric populations, with no curative therapy currently available. Dendritic cells (DCs) are pivotal in initiating Th2 polarization during asthmatic responses, though molecular mechanisms governing DC activation remain incompletely elucidated. As a constituent of the membrane palmitoylated protein family, membrane-associated guanylate kinase (MAGUK) p55 subfamily member 7 (MPP7) has potential therapeutic implications for respiratory disorders, yet its specific involvement in asthma pathogenesis requires further investigation. This study aimed to elucidate MPP7’s protective effects against allergic airway inflammation by analyzing its impact on Th2 immune responses and DC functionality. Clinical data revealed notably reduced MPP7 levels in asthmatic patients’ peripheral blood samples. Experimental models using house-dust-mite (HDM)-exposed mice demonstrated that MPP7 deficiency intensified airway inflammatory responses, with pathological manifestations including amplified leukocyte infiltration, heightened Th2 cytokine production, and elevated serum levels of HDM-specific IgE. Notably, MPP7 caused a marked reduction in pulmonary CD11b+CD103− DCs populations while inhibiting DC activation via interference with NF-κB pathway signaling. These results collectively suggest that MPP7 exerts its anti-inflammatory effects through dual mechanisms involving both cellular subset modulation and intracellular signaling pathway inhibition in DCs, positioning it as a promising candidate for managing allergic respiratory disorders and associated immune-mediated conditions.
Data availability
The RNA-seq datasets are available upon public access from the National Center for Biotechnology Information (NCBI, https://www.ncbi.nlm.nih.gov/), under accession numbers PRJNA1347929.
Abbreviations
- AMOT:
-
Angiomotin
- BMDCs:
-
Bone-marrow-derived dendritic cells
- BALF:
-
Bronchoalveolar lavage fuid
- CNTN1:
-
Contactin-1
- CREB:
-
cAMP response element binding protein
- cDC:
-
Conventional/myeloid DCs
- cDC1s:
-
Conventional type 1 DCs
- cDC2s:
-
Conventional type 2 DCs
- DCs:
-
Dendritic cells
- Dlg1:
-
Discs large homolog 1
- EGFR:
-
Epidermal growth factor receptor
- FITC:
-
Fluoresceinisothiocyanate
- FACS:
-
Fluorescence-activated cell sorting
- GINA:
-
The Global Initiative for Asthma
- GO:
-
Gene Ontology
- HDM:
-
House-dust-mite
- H&E:
-
Haematoxylin & eosin
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- MPP7:
-
The MAGUK p55 subfamily member 7
- MPP:
-
The membrane palmitoylated protein
- METRN-β:
-
Meteorin-β
- MARCH1:
-
Membrane-associated RING-CH 1
- pDCs:
-
Plasmacytoid DCs
- PAS:
-
Periodic acid-Schiff
- qPCR:
-
Quantitative PCR
- RNA-seq:
-
RNA sequencing
- RT‑qPCR:
-
Quantitative reverse transcription polymerase chain reaction
- TGF-β:
-
Transforming growth factor β
- Th2:
-
T-helper-2
- WHO:
-
The World Health Organization
- YAP1:
-
Yes-associated protein
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Acknowledgements
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Funding
This work was supported by the Henan Province science and technology research project (242102310121 and 252102311178).
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Contributions
Yingli Men : Writing - original draft, Validation, Methodology, Investigation, Formal analysis, Conceptualization. Yongfeng Chen : Writing - original draft, Validation, Methodology, Investigation, Formal analysis, Conceptualization. Yi Shao : Writing - original draft, Validation, Investigation, Conceptualization. Hui Wang : Writing - original draft, Validation, Investigation, Conceptualization. Guoxue Wu : Validation, Investigation, Conceptualization. Zhenzhen Yang : Visualization, Investigation. Zhaorui Wang : Visualization, Investigation. Dong Liu : Visualization, Investigation. Ping Wang : Visualization, Investigation. Yahui Hu : Visualization, Investigation. Yang Zheng : Supervision, Methodology. Xiaoyan Xu : Supervision, Methodology. Miling Yang : Writing - review & editing, Supervision, Project administration, Data curation, Conceptualization. Huang Jiang : Writing - review & editing, Supervision, Project administration, Data curation, Conceptualization. Yinsen Song : Writing - review & editing, Supervision, Project administration, Data curation, Conceptualization. Cong Ding : Writing - review & editing, Supervision, Project administration, Funding acquisition, Data curation, Conceptualization.
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Men, Y., Chen, Y., Shao, Y. et al. MAGUK p55 subfamily member 7 attenuates allergic airway inflammation by modulating lung dendritic cells functions. Sci Rep (2026). https://doi.org/10.1038/s41598-026-40491-w
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DOI: https://doi.org/10.1038/s41598-026-40491-w
