ArticleProceedings of the National Academy of Sciences of the United States of America2019
STAT6 induces expression of Gas6 in macrophages to clear apoptotic neutrophils and resolve inflammation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 123 citations in OpenAlex.
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- Skin-mimetic bilayer hydrogel normalizes diabetic wound healing by orchestrating inflammatory cell dynamics: An early intervention strategy.Bioactive materials · 2026Article
- Isoleucyl-tRNA synthetase 1 mutation impairs pulmonary surfactant homeostasis by disrupting alveolar macrophage function.Respiratory research · 2026Article
- Gut microbiota-associated leucine elevation promotes cold-induced atherosclerotic plaque formation and instability.Journal of translational medicine · 2026Article
- Neutrophil-guided pro-efferocytic mRNA platform for accelerated diabetic wound repair.Journal of nanobiotechnology · 2026Article
- Non-enzymatic Rnaseh2c orchestrates proliferating macrophage-driven immunosuppression and HCC progression via Cdk9 proliferation axis and CCL2/CCR2-mediated CD8Journal for immunotherapy of cancer · 2026Article
- Innate Immune Function of Neutrophil Cytoplasts Generated Post-Vital NETosis.Research square · 2026Article
- TGM2 Aggravates Acute Pancreatitis by Impairing Macrophage Efferocytosis Through Inhibition of the STAT6-GAS6 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Fermented Lacticaseibacillus Paracasei Cultures Ameliorate Colitis by Modulating Microbiota-Derived Tryptophan Metabolism and Macrophage Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A transient receptor potential vanilloid 1-dependent corneal-trigeminal neuroinflammatory circuit promotes corneal neuropathy.Experimental & molecular medicine · 2026Article
- Estradiol treatment induces both shared and unique gene regulation and networks in adipose cell types of gonadectomized obese XX and XY mice.Biology of sex differences · 2026Article
- Toward precision host-directed immunomodulation in community-acquired pneumonia: a proposed endotype-target-natural-product framework and a roadmap for validation in human lung organoids.Frontiers in medicine · 2026Review
- Squaric Acid Dibutylester Promotes Innate Immune-Driven Hair Growth with CD206JID innovations : skin science from molecules to population health · 2026Article
- RNASEH2C enhances TRAF3IP1 to degrade RAI14 in lysosomes thus hindering macrophage antigen presentation and advancing liver cancer.Cell death & disease · 2025Article
- AXL and MERTK facilitate tissue repair in severe acute pancreatitis via a CCR5-dependent neutrophil and macrophage crosstalk.Cell communication and signaling : CCS · 2025Article
- Targeting inflammation with chimeric antigen receptor macrophages using a signal switch.Nature biomedical engineering · 2025Article
- Heterogeneity of Lung Phagocytes and Clearance of Apoptotic Cells in Lung Injury and Repair.Seminars in respiratory and critical care medicine · 2025Review
- Effect of pirfenidone on pulmonary fibrosis in acute lung injury via the regulation of the miR-34a-5p/TGF-β1/SMAD pathway.Journal of thoracic disease · 2025Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Efferocytosis of apoptotic neutrophils (PMNs) by alveolar macrophages (AMФs) is vital for resolution of inflammation and tissue injury. Here, we investigated the role of AMФ polarization and expression of the efferocytic ligand Gas6 in restoring homeostasis. In the murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI), we observed augmented temporal generation of cytokines IL-4 and TSG6 in bronchoalveolar fluid (BALF). Interestingly, we also observed increased expression of antiinflammatory markers consistent with a phenotype shift in AMФs. In particular, AMФs expressed the efferocytic ligand Gas6. In vitro priming of bone marrow-derived macrophages (BMMФs) with IL-4 or TSG6 also induced MФ transition and expression of Gas6. TSG6- or IL-4-primed BMMФs induced efferocytosis of apoptotic PMNs compared with control BMMФs. Adoptive transfer of TSG6- or IL-4-primed BMMФs i.t. into LPS-challenged mice more rapidly and effectively cleared PMNs in lungs compared with control BMMФs. We demonstrated that expression of Gas6 during AMФ transition was due to activation of the transcription factor signal transducer and activator of transcription-6 (STAT6) downstream of IL-4 or TSG6 signaling. Adoptive transfer of Gas6-depleted BMMФs failed to clear PMNs in lungs following LPS challenge and mice showed severely defective resolution of lung injury. Thus, activation of STAT6-mediated Gas6 expression during macrophage phenotype transition resulting in efferocytosis of PMNs plays a crucial role in the resolution of inflammatory lung injury.
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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.