Journal article
CD97/ADGRE5 attenuates the induction of adaptive type 2 immune responses in allergic asthma
Nature communications, Vol.17(1), p.9226
08/28/2026
DOI: 10.1038/s41467-026-76948-9
PMID: 42660929
Abstract
Allergic asthma results from an uncontrolled type 2 immune response to inhaled allergens. Here, we investigate the function of CD97/ADGRE5, expressed in mouse and human immune and lung epithelial cells, in this disease. Female Cd97−/− mice exhibit an exacerbated asthmatic phenotype across multiple models, primarily due to CD97 loss on immune cells. A single CD97 antibody treatment before allergen sensitization worsens allergic responses, highlighting a role for CD97 in early immune regulation. Post-sensitization, Cd97−/− mice display higher frequencies of lung conventional type 2 and monocyte-derived dendritic cells (DCs). Allergen-pulsed Cd97−/− bone marrow-derived DCs are more activated, promote enhanced proliferation and type 2 cytokine secretion by CD4⁺ OT-II cells, and induce stronger airway inflammation. Consistently, ADGRE5 expression is reduced in airway mucosa-derived mononuclear phagocyte subsets in human asthmatics after allergen-induced exacerbation. These results identify CD97 as an important regulator of DC-driven type 2 allergic responses and a potential target in asthma. Allergic asthma involves different lung cells and mediators. Here, the authors examine the function of CD97/ADGRE5 and show that its absence increases the severity of allergic lung inflammation in mice. Allergen-pulsed Cd97-/- DCs are more activated and promote stronger type 2 immune responses than WT DCs and, in humans, lung DCs from allergen-exposed asthmatics express less CD97 than allergic non-asthmatics.
Details
- Title: Subtitle
- CD97/ADGRE5 attenuates the induction of adaptive type 2 immune responses in allergic asthma
- Creators
- Gabriela Aust - University Hospital LeipzigAnna-Lena Hoh - University Hospital LeipzigJehan Alladina - Harvard UniversityNeal P. Smith - Massachusetts General HospitalFlorian Höhna - Helmholtz Centre for Environmental ResearchBingyu Wang - Helmholtz Centre for Environmental ResearchChristiane Kerner - University Hospital LeipzigMarita Wagner - Helmholtz Centre for Environmental ResearchKnut Krohn - Leipzig UniversityArkadiusz Pierzchalski - Helmholtz Centre for Environmental ResearchNele Häussler - University Hospital LeipzigAlexandra Chloe Villani - Boston, MA USAJosalyn L. Cho - Iowa City, IA USABenjamin D. Medoff - Massachusetts General HospitalAna C. Zenclussen - Helmholtz Centre for Environmental ResearchMatthias Steinert - University Hospital LeipzigJörg Hamann - Amsterdam University Medical CentersMarianne Quaas - University Hospital LeipzigTobias Polte - Helmholtz Centre for Environmental Research
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.17(1), p.9226
- DOI
- 10.1038/s41467-026-76948-9
- PMID
- 42660929
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- Springer Nature
- Grant note
- Deutsche Forschungsgemeinschaft (German Research Foundation): PO731/8-19
The study was funded by the German Research Foundation (DFG) to G.A. (AU132/10-1) and T.P. (PO731/8-19). Funding for this study was provided by NIH grants NIH 5KL2TR002542-04 (J.A.), NIH DP2CA247831 (A.C.V.), NIH UH2AI44434-01 (J.L.C.), and by the US Department of Defense PR150903/W81XWH-16-1-0493 and Sanofi iAward (both BDM). Open Access funding enabled and organized by Projekt DEAL.
- Language
- English
- Date published
- 08/28/2026
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9985221333102771
Metrics
1 Record Views