ArticleNature immunology2020
The angiocrine Rspondin3 instructs interstitial macrophage transition via metabolic-epigenetic reprogramming and resolves inflammatory injury.
Article in Nature immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
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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.
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Who cites it
78 citing papers in PubMed, 111 citations in OpenAlex.
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- Angiogenesis in Lung Regeneration and Aging.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Maternal Exercise and Offspring Cardiac Regenerative Potential: Roles of Apelin and α-Ketoglutarate.Biology · 2026Review
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- Angiocrine factors in tumor microenvironment: bidirectional crosstalk, mechanistic insights, and therapeutic strategies.Journal of translational medicine · 2026Review
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- Sex-specific impact of early life stress on adult lung inflammatory response after LPS and Poly I:C exposures.Brain, behavior, & immunity - health · 2026Article
- Hypothermic machine perfusion protects DCD graft liver from ischemia‑reperfusion injury by enhancing macrophage efferocytosis via KLF2‑NLRP3 signaling.International journal of molecular medicine · 2026Article
- KIF11 prevents retinal endothelial ferroptosis in familial exudative vitreoretinopathy by inhibiting phosphorylation-driven PRDX1 phase separation.Nature communications · 2026Article
- Source-renewing ectopic ApoB-TRL lipolysis in non-resolving ARDS: a testable spatial hypothesis.Frontiers in immunology · 2026Article
- The immune dysregulation of fibrosis: insights into immune-fibrotic crosstalk and potential therapeutic targets.Frontiers in immunology · 2026Review
- Mechanisms and therapeutics of immunometabolic reprogramming driving macrophage-ECs interactions in sepsis-associated ARDS from the gut-lung axis perspective.Frontiers in immunology · 2026Review
- The impact of macrophage metabolism on idiopathic pulmonary fibrosis development and treatment prospectives.Frontiers in immunology · 2026Review
- NIR-II Responsive Multifunctional Scaffold Enabling "Kill-Modulation-Build" Synergistic Therapy for Infectious Bone Defects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Single-cell spatial atlas of smoking-induced changes in human gingival tissues.International journal of oral science · 2025Article
- Effects of Alpha-Ketoglutarate Supplementation on Growth Performance, Diarrhea Incidence, Plasma Amino Acid, and Nutrient Digestibility in Weaned Piglets.Animals : an open access journal from MDPI · 2025Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Macrophages demonstrate remarkable plasticity that is essential for host defense and tissue repair. The tissue niche imprints macrophage identity, phenotype and function. The role of vascular endothelial signals in tailoring the phenotype and function of tissue macrophages remains unknown. The lung is a highly vascularized organ and replete with a large population of resident macrophages. We found that, in response to inflammatory injury, lung endothelial cells release the Wnt signaling modulator Rspondin3, which activates β-catenin signaling in lung interstitial macrophages and increases mitochondrial respiration by glutaminolysis. The generated tricarboxylic acid cycle intermediate α-ketoglutarate, in turn, serves as the cofactor for the epigenetic regulator TET2 to catalyze DNA hydroxymethylation. Notably, endothelial-specific deletion of Rspondin3 prevented the formation of anti-inflammatory interstitial macrophages in endotoxemic mice and induced unchecked severe inflammatory injury. Thus, the angiocrine-metabolic-epigenetic signaling axis specified by the endothelium is essential for reprogramming interstitial macrophages and dampening inflammatory injury.
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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.