ArticleFrontiers of medicine2024
Adenosine deaminase 2 regulates the activation of the toll-like receptor 9 in response to nucleic acids.
Article in Frontiers of medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed.
- Adenosine deaminase type 2 deficiency: From rare to common.Journal of human immunity · 2026Review
- Anifrolumab, a potential treatment for ADA2 deficiency.RMD open · 2026Article
- ADA2-deficient cells exhibit increased levels of cell death and metabolic disturbances.Cell death discovery · 2026Article
- Diagnostic Implications and Correlates of Plasma Adenosine Deaminase 2 Activity and ADA2 Variants.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Gene therapy supports long-term reconstitution of patient hematopoietic stem cells in deficiency of adenosine deaminase 2.Molecular therapy. Methods & clinical development · 2025Article
- Inhibition of lysosomal degradation increases expression of mutant ADA2 in DADA2 monocytes.The Journal of allergy and clinical immunology · 2025Article
- Spondyloenchondrodysplasia: An enigmatic immuno-osseus type I interferonopathy.Journal of human immunity · 2025Article
- Getting to know adenosine deaminase 2 deficiency inside and out.The Journal of allergy and clinical immunology · 2025Review
- Intracellular concentration of ADA2 is a marker for monocyte differentiation and activation.Frontiers of medicine · 2025Article
- A rapid antigen test to detect adenosine deaminase 2 (ADA2) in biological fluids and its application in clinical diagnostics.Frontiers in immunology · 2025Article
- Developing and validating anti-ADA2 single-chain antibodies coupled to alkaline phosphatase for diagnosing pleural tuberculosis.Frontiers in immunology · 2025Article
- Targeting CD73 and correcting adenosinergic signaling in critically ill patients.Frontiers in pharmacology · 2025Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human cells contain two types of adenosine deaminases (ADA) each with unique properties: ADA1, which is present in all cells where it modulates intracellular functions and extracellular signaling, and ADA2, which is secreted by immune cells. The exact intracellular functions of ADA2 remain undetermined and less defined than those of ADA1. ADA2 has distinct characteristics, such as low adenosine affinity, heparin-binding ability, and putative lysosomal entry. Here, we confirm that ADA2 is a lysosomal protein that binds toll-like receptor 9 (TLR9) agonists, specifically CpG oligodeoxynucleotides (CpG ODNs). We show that interferon-alpha (IFN-α) is secreted in response to TLR9 activation by CpG ODNs and natural DNA and markedly increases when ADA2 expression is downregulated in plasmacytoid dendritic cells (pDCs). Additionally, the pretreatment of pDCs with RNA further stimulates IFN-α secretion by pDCs after activation with CpG ODNs. Our findings indicate that ADA2 regulates TLR9 responses to DNA in activated pDCs. In conclusion, decreasing ADA2 expression or blocking it with specific oligonucleotides can enhance IFN-α secretion from pDCs, improving immune responses against intracellular infections and cancer.
Indexed as
Identifiers
39078537What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.