ArticleThe Journal of clinical investigation2016
p21 mediates macrophage reprogramming through regulation of p50-p50 NF-κB and IFN-β.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
What it found
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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
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Advances in the research of the role of macrophage/microglia polarization-mediated inflammatory response in spinal cord injury.Frontiers in immunology · 2022Pooled it
- p21 (CDKN1A) Is the Major Driver of Sulforaphane-Mediated Reduction in SAMHD1 T592 Phosphorylation in Macrophages.Biomolecules · 2026Article
- The alternative polyadenylation factor CFIm25 orchestrates macrophage antibacterial activity againstInfection and immunity · 2026Article
- Induction of senescence like macrophages by hepatocellular carcinoma cells in vitro.Discover oncology · 2026Article
- PRMT6 inhibition or deficiency attenuates diabetic neuropathic pain in male mice and is associated with reduced spinal neuroinflammation, microgliosis, and altered p53-p21 signaling.Journal of neuroinflammation · 2026Article
- Adipose extracellular vesicles carrying miR-210-3p drive macrophage inflammation and nicotine-induced atherosclerosis.iScience · 2026Article
- MyD88-mediated chimaeric antigen receptor macrophages suppress brain metastasis using target-specific phagocytosis.Nature biomedical engineering · 2026Article
- Sepsis induces long-term reprogramming of human HSPCs and drives myeloid dysregulation in sepsis survivors.Journal of inflammation (London, England) · 2026Article
- When to initiate immunomodulatory therapy in sepsis.Frontiers in immunology · 2026Review
- The Role of CDKs in the Regulation of the Monocyte/Macrophage Immune Response.Current medicinal chemistry · 2026Review
- Crosstalk of mitochondrial dysfunction and macrophage polarization in sepsis.Frontiers in immunology · 2026Review
- Continuous adipose-derived stem cell therapy from the neonatal stage effectively reduces Duchenne muscular dystrophy symptoms in rats.Stem cell research & therapy · 2025Article
- Gas Bubbles from Biodegradable Magnesium Implants Convey Mechanical Cues and Promote Immune Cell Stimulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Glucosylated cholesterol accumulates in atherosclerotic lesions and impacts macrophage immune response.Journal of lipid research · 2025Article
- Nuclear mitochondrial acetyl-CoA acetyltransferase 1 orchestrates natural killer cell-dependent antitumor immunity in colorectal cancer.Signal transduction and targeted therapy · 2025Article
- Senescent cell reduction does not improve recovery in mice under experimental autoimmune encephalomyelitis (EAE) induced demyelination.Journal of neuroinflammation · 2025Article
- Pathophysiology-Directed Engineering of a Combination Nanoanalgesic for Neuropathic Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Role of macrophage polarization in diabetic foot ulcer healing: A bibliometric study.World journal of diabetes · 2025Article
- The Dual Role of Cellular Senescence in Macrophages: Unveiling the Hidden Driver of Age-Related Inflammation in Kidney Disease.International journal of biological sciences · 2025Review
- Ulcerative colitis: the healing power of macrophages.Tissue barriers · 2025Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
M1 and M2 macrophage phenotypes, which mediate proinflammatory and antiinflammatory functions, respectively, represent the extremes of immunoregulatory plasticity in the macrophage population. This plasticity can also result in intermediate macrophage states that support a balance between these opposing functions. In sepsis, M1 macrophages can compensate for hyperinflammation by acquiring an M2-like immunosuppressed status that increases the risk of secondary infection and death. The M1 to M2 macrophage reprogramming that develops during LPS tolerance resembles the pathological antiinflammatory response to sepsis. Here, we determined that p21 regulates macrophage reprogramming by shifting the balance between active p65-p50 and inhibitory p50-p50 NF-κB pathways. p21 deficiency reduced the DNA-binding affinity of the p50-p50 homodimer in LPS-primed and -rechallenged macrophages, impairing their ability to attenuate IFN-β production and acquire an M2-like hyporesponsive status. High p21 levels in sepsis patients correlated with low IFN-β expression, and p21 knockdown in human monocytes corroborated its role in IFN-β regulation. The data demonstrate that p21 adjusts the equilibrium between p65-p50 and p50-p50 NF-κB pathways to mediate macrophage plasticity in LPS tolerance. Identifying p21-related pathways involved in monocyte reprogramming may lead to potential targets for sepsis treatment.
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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.