ArticleMolecular and cellular biology2015
Human monocyte recognition of adenosine-based cyclic dinucleotides unveils the A2a Gαs protein-coupled receptor tonic inhibition of mitochondrially induced cell death.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Genetic deletion of adenosine AGeroScience · 2026Article
- STING agonists trigger monocyte death via apoptosis, pyroptosis, caspase-8 activation and mitochondrial dysfunction.Cell death discovery · 2025Article
- NetLnc: A Network-Based Computational Framework to Identify Immune Checkpoint-Related lncRNAs for Immunotherapy Response in Melanoma.International journal of molecular sciences · 2025Article
- Pan-cancer evaluation of regulated cell death to predict overall survival and immune checkpoint inhibitor response.NPJ precision oncology · 2024Article
- Identifying immune checkpoint-related lncRNA biomarkers for immunotherapy response and prognosis in cancers.Scientific data · 2023Article
- Identification of the molecular subtype and prognostic characteristics of pancreatic cancer based on CD8 + T cell-related genes.Cancer immunology, immunotherapy : CII · 2023Article
- Signal strength of STING activation determines cytokine plasticity and cell death in human monocytes.Scientific reports · 2022Article
- Correlation between Tumor Microenvironment and Immune Subtypes Based on CD8 T Cells Enhancing Personalized Therapy of Gastric Cancer.Journal of oncology · 2022Article
- Stimulatory and inhibitory activity of STING ligands on tumor-reactive human gamma/delta T cells.Oncoimmunology · 2022Article
- Mitochondrial inhibitors circumvent adaptive resistance to venetoclax and cytarabine combination therapy in acute myeloid leukemia.Nature cancer · 2021Article
- Tumor-Infiltrating Immune-Related Long Non-Coding RNAs Indicate Prognoses and Response to PD-1 Blockade in Head and Neck Squamous Cell Carcinoma.Frontiers in immunology · 2021Article
- Extracellular cyclic dinucleotides induce polarized responses in barrier epithelial cells by adenosine signaling.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclic dinucleotides are important messengers for bacteria and protozoa and are well-characterized immunity alarmins for infected mammalian cells through intracellular binding to STING receptors. We sought to investigate their unknown extracellular effects by adding cyclic dinucleotides to the culture medium of freshly isolated human blood cells in vitro. Here we report that adenosine-containing cyclic dinucleotides induce the selective apoptosis of monocytes through a novel apoptotic pathway. We demonstrate that these compounds are inverse agonist ligands of A2a, a Gαs-coupled adenosine receptor selectively expressed by monocytes. Inhibition of monocyte A2a by these ligands induces apoptosis through a mechanism independent of that of the STING receptors. The blockade of basal (adenosine-free) signaling from A2a inhibits protein kinase A (PKA) activity, thereby recruiting cytosolic p53, which opens the mitochondrial permeability transition pore and impairs mitochondrial respiration, resulting in apoptosis. A2a antagonists and inverse agonist ligands induce apoptosis of human monocytes, while A2a agonists are antiapoptotic. In vivo, we used a mock developing human hematopoietic system through NSG mice transplanted with human CD34(+) cells. Treatment with cyclic di-AMP selectively depleted A2a-expressing monocytes and their precursors via apoptosis. Thus, monocyte recognition of cyclic dinucleotides unravels a novel proapoptotic pathway: the A2a Gαs protein-coupled receptor (GPCR)-driven tonic inhibitory signaling of mitochondrion-induced cell death.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.