Immunoregulatory properties of cell free DNA
Cell free DNA (cfDNA) is detectable at low concentrations in the plasma of healthy subjects and at high concentrations in disorders characterized by a high rate of necrotic events, such as tumors and vasculitis, leading to the release of necrotic DNA into the surrounding tissue and the bloodstream. Although cfDNA may act as a danger signal by binding to DNA sensors, triggering inflammation and immune responses, elevated cfDNA concentrations instead may exert immunoregulatory activities. Here, we show that exogenously administered cfDNA mediates immunoregulatory functions in vivo, in particular, it protects lupus-prone mice from disease progression and favors tumor growth in tumor-challenged mice. Our data suggest that cfDNA mediates immune regulatory activities by directly interacting with MHC class II molecules on antigen-presenting cells and through recruitment of regulatory T cells. This study unveils unprecedented biologic functions of cfDNA with significant pathogenic relevance and remarkable implications for the treatment of cancer patients.
Authors
- Giuseppina Astone (ORCID: https://orcid.org/0000-0003-4206-3491)
- Daniela Fenoglio (ORCID: https://orcid.org/0000-0001-9532-6473)
- Francesca Ferrera (ORCID: https://orcid.org/0000-0003-1172-5616)
- Gianluca Damonte (ORCID: https://orcid.org/0000-0001-8769-2051)
- Giuseppina Conteduca
- Samuele Tardito (ORCID: https://orcid.org/0000-0002-5272-5228)
- Raffaele De Palma (ORCID: https://orcid.org/0000-0001-9070-8878)
- Gilberto Filaci (ORCID: https://orcid.org/0000-0001-6445-8414)
- Annalisa Salis
- Elena Cichero (ORCID: https://orcid.org/0000-0001-6781-9289)
- Tiziana Altosole (ORCID: https://orcid.org/0000-0002-8729-0834)
- Valentina Rigo (ORCID: https://orcid.org/0000-0002-2032-3929)
- Paola Fossa (ORCID: https://orcid.org/0000-0001-9386-0445)
- Leonardo Arpesella (ORCID: https://orcid.org/0009-0006-5779-0981)
- Alessia Parodi (ORCID: https://orcid.org/0000-0001-8476-8241)
- Giorgio Inghirami (ORCID: https://orcid.org/0000-0002-5298-6516)
- Cinzia Bernardi
- Chiara Marini
- Laura Camporesi
- Andrea Lagazio
- Andrea Pigozzo
Institutions
- Children's National (US)
- Cornell University (US)
- Alstom (France) (FR)
- Ospedale Policlinico San Martino (IT)
- University of Genoa (IT)
Publication Details
- Journal
- Cellular and Molecular Life Sciences
- Published
- 2025-08-26
- DOI
- https://doi.org/10.1007/s00018-025-05862-y
- Citations
- 1
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- Università degli Studi di Genova