CD97/ADGRE5 attenuates the induction of adaptive type 2 immune responses in allergic asthma
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.
Authors
- Neal P. Smith (ORCID: https://orcid.org/0000-0003-1394-3158)
- Marianne Quaas (ORCID: https://orcid.org/0000-0002-2781-1968)
- Benjamin D. Medoff (ORCID: https://orcid.org/0000-0002-2558-0449)
- Marita Wagner
- Christina Schofield (ORCID: https://orcid.org/0000-0002-0367-4495)
- Knut Krohn (ORCID: https://orcid.org/0000-0001-8110-1273)
- Anna-Lena Hoh
- Tobias Polte
- Alexandra–Chloé Villani (ORCID: https://orcid.org/0000-0001-7461-0408)
- Ana Claudia Zenclussen (ORCID: https://orcid.org/0000-0003-3544-4552)
- Jörg Hamann (ORCID: https://orcid.org/0000-0002-9448-1727)
- Arkadiusz Pierzchalski
- Christiane Kerner
- Jehan Alladina (ORCID: https://orcid.org/0000-0003-0136-6859)
- Gabriela Aust (ORCID: https://orcid.org/0000-0002-4670-4543)
- Bingyu Wang
- Matthias Steinert
- Florian Höhna
- Nele Häussler
Institutions
- University of Iowa (US)
- Harvard University (US)
- Helmholtz Centre for Environmental Research (DE)
- Massachusetts General Hospital (US)
- University Hospital Leipzig (DE)
- Amsterdam University Medical Centers (NL)
- Martin Luther University Halle-Wittenberg (DE)
- University of Amsterdam (NL)
- Leipzig University (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-08-27
- DOI
- https://doi.org/10.1038/s41467-026-76948-9
- Primary Topic
- Receptor Mechanisms and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Defense
- Sanofi
- Deutsche Forschungsgemeinschaft
- National Institutes of Health