ArticleThe Journal of experimental medicine2013
IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 244 papers.
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Who cites it
244 citing papers in PubMed, 386 citations in OpenAlex.
- A Post-NGP Mitsuokella jalaludinii as a Therapeutic Candidate for Gout.MicrobiologyOpen · 2026Article
- A workflow to reduce red blood cell autofluorescence for imaging IL-4/IL-4R interactions in the inflamed lung.Biochemistry and biophysics reports · 2026Article
- Mitochondrial profiling across macrophage states reveals inhibition of IL-4/IL-13 reprogramming by the integrated stress response.Science advances · 2026Article
- Heritable single-cell gene expression states shape functional variability in innate immune responses.bioRxiv : the preprint server for biology · 2026Article
- Emerging biomedical and pharmaceutical strategies for the treatment of atherosclerosis: from conventional lipid-lowering therapy to nanomedicine.Journal of applied biomedicine · 2026Review
- Basophils drive the resolution and promote wound healing in adult and aged mice.The Journal of experimental medicine · 2026Article
- Acute and resolving inflammation differentially regulates beta cell function in mice via interactions between peritoneal and islet-associated macrophages.Diabetologia · 2026Article
- Article
- IL-4/STAT6-signaling Influences Local Inflammation and Regeneration Processes During Acute Pancreatitis and Promotes Fibrosis by a Direct Activation of Pancreatic Fibroblasts During Chronic Pancreatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tumor-associated macrophages display differential protein cargo sorting in extracellular vesicles associated with poor survival in ovarian cancer.Molecular medicine (Cambridge, Mass.) · 2026Article
- IFI44 Orchestrates an IL-10-Driven M2 Macrophage Program in Breast Cancer: An Immune Prognostic Signature.Breast cancer (Dove Medical Press) · 2026Article
- Neuregulin-1 promotes early regenerative and autophagic responses after ischemic stroke via spatial proteomics.Frontiers in cellular neuroscience · 2026Article
- Targeting Macrophage-Mediated Mechanisms in Sepsis-Induced Cardiomyopathy: From Pathophysiology to Therapeutic Strategies.Journal of inflammation research · 2026Review
- Persistent myeloid cell reprogramming despite miltefosine treatment in leishmania-infected macaques.iScience · 2025Article
- CD154 Restricts Helminth-Induced Macrophage Polarisation and Proliferation While Promoting Tissue Residence.Parasite immunology · 2025Article
- A novel neutrophil extracellular trap-related gene signature for predicting glioblastoma prognosis.Scientific reports · 2025Article
- CD206Circulation · 2025Article
- Macrophage IL-4 polarization is restricted by soluble CD40 agonists and antigen-induced CD154 but not by constitutive CD154 expressed by CD4+ T cells.Journal of leukocyte biology · 2025Article
- Kupffer cell and recruited macrophage heterogeneity orchestrate granuloma maturation and hepatic immunity in visceral leishmaniasis.Nature communications · 2025Article
- A functional cardiac patch promotes cardiac repair by modulating the CCR2Cell reports. Medicine · 2025Article
184 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Macrophages (MΦs) colonize tissues during inflammation in two distinct ways: recruitment of monocyte precursors and proliferation of resident cells. We recently revealed a major role for IL-4 in the proliferative expansion of resident MΦs during a Th2-biased tissue nematode infection. We now show that proliferation of MΦs during intestinal as well as tissue nematode infection is restricted to sites of IL-4 production and requires MΦ-intrinsic IL-4R signaling. However, both IL-4Rα-dependent and -independent mechanisms contributed to MΦ proliferation during nematode infections. IL-4R-independent proliferation was controlled by a rise in local CSF-1 levels, but IL-4Rα expression conferred a competitive advantage with higher and more sustained proliferation and increased accumulation of IL-4Rα(+) compared with IL-4Rα(-) cells. Mechanistically, this occurred by conversion of IL-4Rα(+) MΦs from a CSF-1-dependent to -independent program of proliferation. Thus, IL-4 increases the relative density of tissue MΦs by overcoming the constraints mediated by the availability of CSF-1. Finally, although both elevated CSF1R and IL-4Rα signaling triggered proliferation above homeostatic levels, only CSF-1 led to the recruitment of monocytes and neutrophils. Thus, the IL-4 pathway of proliferation may have developed as an alternative to CSF-1 to increase resident MΦ numbers without coincident monocyte recruitment.
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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.