ArticleProceedings of the National Academy of Sciences of the United States of America2012
Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 597 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
597 citing papers in PubMed, 969 citations in OpenAlex.
- Autologous macrophage therapy for liver cirrhosis: a phase 2 open-label randomized controlled trial.Nature medicine · 2025Trial
- Antifibrotic monocyte activation by nanoparticles resolves murine pulmonary fibrosis.Biomaterials · 2026Article
- Single-cell RNA sequencing identifies a proinflammatory S100a8/a9Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- A human single-cell atlas identifies OLR1Nature genetics · 2026Article
- Macrophage heterogeneity in organ fibrosis in the era of single-cell omics.Molecular biology reports · 2026Review
- Allogeneic skin transplantation induces transient fibrosis that undergoes spontaneous regression in newts.Inflammation and regeneration · 2026Article
- Impact of pharmacological sGC stimulation with Riociguat in experimental models of liver disease regression.Hepatology international · 2026Article
- Fibroblast-derived CCL2 orchestrates immune responses and defends against Staphylococcus aureus skin infection.Cellular & molecular immunology · 2026Article
- A pathogenic CD8⁺ TNature communications · 2026Article
- Macrophage FOLR2 drives liver fibrosis via intercellular engagement of TGFβRII.Acta pharmacologica Sinica · 2026Article
- Liver Fibrosis and Purinergic Signaling: Autocrine-Paracrine Role of ATP in Liver Damage.International journal of molecular sciences · 2026Review
- Liver Macrophages in the Pathogenesis of Viral Hepatitis.Current issues in molecular biology · 2026Review
- Reprogramming macrophages to treat liver diseases.Hepatology (Baltimore, Md.) · 2026Review
- Endothelial cell glycogen synthase kinase 3β promotes lipotoxic endotheliopathy and liver inflammation in MASH.JCI insight · 2026Article
- In vivo generation of fibrolytic macrophages via LNP-CSF1 mRNA attenuates liver fibrosis.Journal of nanobiotechnology · 2026Article
- Integrated multi-omics identifies distinct macrophage alterations during progression of metabolic dysfunction-associated steatohepatitis.Nature genetics · 2026Article
- [Research progress on cellular senescence and liver diseases].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- ADAMTS4 elicits myeloid-derived immune cell recruitment and liver fibrogenesis in metabolic dysfunction-associated steatotic liver disease.Signal transduction and targeted therapy · 2026Article
- Stabilin‑1: An immunoregulatory scavenger receptor in inflammation and tissue homeostasis (Review).Molecular medicine reports · 2026Review
- CD47 Blockade Reprograms the Monocyte-Macrophage Axis to Promote Inflammation Resolution in Atherosclerosis.bioRxiv : the preprint server for biology · 2026Article
537 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
Although macrophages are widely recognized to have a profibrotic role in inflammation, we have used a highly tractable CCl(4)-induced model of reversible hepatic fibrosis to identify and characterize the macrophage phenotype responsible for tissue remodeling: the hitherto elusive restorative macrophage. This CD11B(hi) F4/80(int) Ly-6C(lo) macrophage subset was most abundant in livers during maximal fibrosis resolution and represented the principle matrix metalloproteinase (MMP) -expressing subset. Depletion of this population in CD11B promoter-diphtheria toxin receptor (CD11B-DTR) transgenic mice caused a failure of scar remodeling. Adoptive transfer and in situ labeling experiments showed that these restorative macrophages derive from recruited Ly-6C(hi) monocytes, a common origin with profibrotic Ly-6C(hi) macrophages, indicative of a phenotypic switch in vivo conferring proresolution properties. Microarray profiling of the Ly-6C(lo) subset, compared with Ly-6C(hi) macrophages, showed a phenotype outside the M1/M2 classification, with increased expression of MMPs, growth factors, and phagocytosis-related genes, including Mmp9, Mmp12, insulin-like growth factor 1 (Igf1), and Glycoprotein (transmembrane) nmb (Gpnmb). Confocal microscopy confirmed the postphagocytic nature of restorative macrophages. Furthermore, the restorative macrophage phenotype was recapitulated in vitro by the phagocytosis of cellular debris with associated activation of the ERK signaling cascade. Critically, induced phagocytic behavior in vivo, through administration of liposomes, increased restorative macrophage number and accelerated fibrosis resolution, offering a therapeutic strategy to this orphan pathological process.
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.