ArticleBlood2022
Unique characteristics of lung-resident neutrophils are maintained by PGE2/PKA/Tgm2-mediated signaling.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- p38 MAPK signaling in chronic obstructive pulmonary disease pathogenesis and inhibitor therapeutics.Cell communication and signaling : CCS · 2023Pooled it
- Transglutaminase 2 regulates innate immunity: mechanisms and therapeutic implications.Oncoimmunology · 2026Review
- Identification of potential biological biomarkers for acute ischemic stroke based on integrated bioinformatics analyses.BMC neurology · 2026Article
- Impact of NSAID type, initiation timing, duration and dose on clinical outcomes of immunotherapy in NSCLC: a multicenter two-cohort study.Journal for immunotherapy of cancer · 2026Observational
- Neutrophil heterogeneity in Kawasaki disease and multisystem inflammatory syndrome in children.Pediatric research · 2026Review
- Mitochondrial-related biomarkers as the diagnostic markers in sepsis induced acute respiratory distress syndrome.European journal of medical research · 2026Article
- Neutrophil Plasticity in Airway Disease: Balancing Damage and Repair.Journal of innate immunity · 2026Review
- The neutrophil collective.Cell · 2025Review
- Discovery of intrahepatic CD103Experimental & molecular medicine · 2025Article
- TGM2 Enhances Hypobaric Hypoxia-mediated Brain Injury Via Regulating NLRP3/GSDMD Signaling.Neurochemical research · 2025Article
- γδCellular & molecular immunology · 2025Article
- Exploring Neutrophil Heterogeneity and Plasticity in Health and Disease.Biomedicines · 2025Review
- Effect of Multidimensional Integrated Lung Protection Measures in Elderly Patients With Fragile Lungs or Combined Lung Dysfunction by Regulating AMPK/SIRT1 Pathway.Journal of cellular and molecular medicine · 2025Article
- Tissue-resident immune cells: from defining characteristics to roles in diseases.Signal transduction and targeted therapy · 2025Review
- The Importance of Lung Innate Immunity During Health and Disease.Pathogens (Basel, Switzerland) · 2025Review
- Neutrophil diversity and function in health and disease.Signal transduction and targeted therapy · 2024Review
- The diverse roles of neutrophils from protection to pathogenesis.Nature immunology · 2024Review
- Tissue-Specific Immune Transcriptional Signatures in the Bordering Tissues of the Mouse Retina and Brain.Investigative ophthalmology & visual science · 2024Article
- CD200RCellular & molecular immunology · 2024Article
- RGS20 promotes non-small cell lung carcinoma proliferation via autophagy activation and inhibition of the PKA-Hippo signaling pathway.Cancer cell international · 2024Article
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung-resident neutrophils need to be tightly regulated to avoid degranulation- and cytokine-associated damage to fragile alveolar structures that can lead to fatal outcomes. Here we show that lung neutrophils (LNs) express distinct surface proteins and genes that distinguish LNs from bone marrow and blood neutrophils. Functionally, LNs show impaired migratory activity toward chemoattractants and produce high levels of interleukin-6 (IL-6) at steady state and low levels of tumor necrosis factor-α in response to lipopolysaccharide (LPS) challenge. Treating bone marrow neutrophils with bronchoalveolar lavage fluid or prostaglandin E2 induces LN-associated characteristics, including the expression of transglutaminase 2 (Tgm2) and reduced production of inflammatory cytokines upon LPS challenge. Neutrophils from Tgm2-/- mice release high levels of inflammatory cytokines in response to LPS. Lung damage is significantly exacerbated in Tgm2-/- mice in an LPS-induced acute respiratory distress syndrome model. Collectively, we demonstrate that prostaglandin E2 is a key factor for the generation of LNs with unique immune suppressive characteristics, acting through protein kinase A and Tgm2, and LNs play essential roles in protection of the lungs against pathogenic inflammation.
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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.