ADA2 is a lysosomal deoxyadenosine deaminase acting on DNA involved in regulating TLR9-mediated immune sensing of DNA
Abstract: Although adenosine deaminase 2 (ADA2) is considered an extracellular ADA, evidence questions the physiological relevance of this activity. Our study reveals that ADA2 localizes within the lysosomes, where it is targeted through modifications of its glycan structures. We show that ADA2 interacts with DNA molecules, altering their sequences by converting deoxyadenosine (dA) to deoxyinosine (dI). We characterize its DNA substrate preferences and provide data suggesting that DNA, rather than free adenosine, is its natural substrate. Finally, we demonstrate that dA-to-dI editing of DNA molecules and ADA2 regulate lysosomal immune sensing of nucleic acids (NAs) by modulating Toll-like receptor 9 (TLR9) activation. Our results describe a mechanism involved in the complex interplay between NA metabolism and immune response, possibly impacting ADA2 deficiency (DADA2) and other diseases involving this pathway, including autoimmune diseases, cancer, or infectious diseases
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Cell reports. - 43, 11 (2024) , 114899, ISSN: 2211-1247
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2024
- Creator
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Greiner-Tollersrud, Ole Kristian
Krausz, Máté
Spahiu, Ambra
Hübscher, Katrin
Goschin, Andreas
Baasch, Sebastian
Henneke, Philipp
Grimbacher, Bodo
Bartok, Eva
Alseth, Ingrun
Warncke, Max
Proietti, Michele
- DOI
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10.1016/j.celrep.2024.114899
- URN
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urn:nbn:de:bsz:25-freidok-2585893
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
- 15.08.2025, 7:31 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Greiner-Tollersrud, Ole Kristian
- Krausz, Máté
- Spahiu, Ambra
- Hübscher, Katrin
- Goschin, Andreas
- Baasch, Sebastian
- Henneke, Philipp
- Grimbacher, Bodo
- Bartok, Eva
- Alseth, Ingrun
- Warncke, Max
- Proietti, Michele
- Universität
Time of origin
- 2024
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