ArticleImmunity2016
Metabolic Reprogramming Mediated by the mTORC2-IRF4 Signaling Axis Is Essential for Macrophage Alternative Activation.
Article in Immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 398 papers, 3 of them syntheses that pooled it.
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
398 citing papers in PubMed, 3 syntheses or guidelines pooled it, 657 citations in OpenAlex.
- From mechanism to therapy: advances in macrophage polarisation and targeted intervention in osteosarcoma.Frontiers in immunology · 2026Pooled it
- Using meta-analysis and machine learning to investigate the transcriptional response of immune cells to Leishmania infection.PLoS neglected tropical diseases · 2024Pooled it
- The role of cluster of differentiation 163-positive macrophages in wound healing: a preliminary study and a systematic review.Archives of dermatological research · 2023Pooled it
- Alox15 restrains glycolysis to support M2 macrophage effector function during helminth immunity.The Journal of experimental medicine · 2026Article
- Platelet-derived serotonin epigenetically programs macrophage alternative activation to orchestrate type 2 airway inflammation.Cellular & molecular immunology · 2026Article
- Coenzyme A activates TLR4 and enhances alternative macrophage activation in line with MyD88 agonism.EMBO reports · 2026Article
- Article
- The role of mTORC2/RICTOR in immune cells and inflammatory diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Review
- Exploratory single-nucleus multiomics analysis of myeloid cell states associated with neoadjuvant chemotherapy response in pancreatic ductal adenocarcinoma.Clinical and translational medicine · 2026Article
- Mitochondrial profiling across macrophage states reveals inhibition of IL-4/IL-13 reprogramming by the integrated stress response.Science advances · 2026Article
- Transfer RNA Modifications in the Immune System Participate in Disease Pathogenesis.International journal of molecular sciences · 2026Review
- Mitochondrial Metabolic Reprogramming and Skin Immune Homeostasis: From Basic Mechanisms to Therapeutic Perspectives.Immune network · 2026Review
- Review
- GRP75 sustains CD8Cell death and differentiation · 2026Article
- Metabolic regulation of macrophage polarization in myocardial infarction: from mechanisms to targeted therapies.Journal of translational medicine · 2026Review
- Precision engineering of macrophage reprogramming with RNA interference-loaded lipid nanoparticles: a game-changer in cancer immunotherapy.Drug delivery and translational research · 2026Review
- Depot-Specific White Adipose Tissue Remodeling Supports Non-Thermogenic Metabolic Homeostasis During Shallow Hibernation in Raccoon Dogs.International journal of molecular sciences · 2026Article
- SREBP2 promotes macrophage alternative activation and allergic airway inflammation independent of cholesterol biosynthesis.Cell death & disease · 2026Article
- Neutrophil extracellular traps promote macrophage activation through Toll-like receptor engagement and PKA and NF-kB signaling pathways.Cell communication and signaling : CCS · 2026Article
338 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
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Macrophage activation status is intrinsically linked to metabolic remodeling. Macrophages stimulated by interleukin 4 (IL-4) to become alternatively (or, M2) activated increase fatty acid oxidation and oxidative phosphorylation; these metabolic changes are critical for M2 activation. Enhanced glucose utilization is also characteristic of the M2 metabolic signature. Here, we found that increased glucose utilization is essential for M2 activation. Increased glucose metabolism in IL-4-stimulated macrophages required the activation of the mTORC2 pathway, and loss of mTORC2 in macrophages suppressed tumor growth and decreased immunity to a parasitic nematode. Macrophage colony stimulating factor (M-CSF) was implicated as a contributing upstream activator of mTORC2 in a pathway that involved PI3K and AKT. mTORC2 operated in parallel with the IL-4Rα-Stat6 pathway to facilitate increased glycolysis during M2 activation via the induction of the transcription factor IRF4. IRF4 expression required both mTORC2 and Stat6 pathways, providing an underlying mechanism to explain how glucose utilization is increased to support M2 activation.
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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.