2025
Humanization of CD47 enables development of functional human neutrophils via postirradiation remodeling of the bone marrow.
Sefik E, Philbrick W, Zhang F, Agrawal K, Van Lee B, Sam J, Karatepe K, Zheng Y, Liang K, Peng S, Mirza H, Rangavajhula A, Simon P, Arun N, Babu P, Eynon E, Chiorazzi M, Shan L, Halene S, Luo H, Rongvaux A, Kluger Y, Flavell R. Humanization of CD47 enables development of functional human neutrophils via postirradiation remodeling of the bone marrow. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2426546122. PMID: 40956886, PMCID: PMC12478129, DOI: 10.1073/pnas.2426546122.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone MarrowCD47 AntigenHumansMiceMice, Inbred C57BLMice, TransgenicMyelopoiesisNeutrophilsConceptsBone marrowHuman CD47Human granulocyte-macrophage progenitorsHuman immune developmentMature human monocytesHuman neutrophilsHumanized mouse modelNeutrophil extracellular trap formationHuman hematopoietic stemGranulocyte-macrophage progenitorsHuman M-CSFHuman immune responseGenetically modified miceResponse to inflammationExtracellular trap formationHuman bone marrowCD47 promoterHuman immune systemPhysiological levelsNK cellsHumanized miceDendritic cellsHematopoietic stemMyeloid lineageHuman hematopoiesisInvestigating cytotoxic and inflammatory human IL-7 receptor low effector memory CD8+ T cells in lupus
Lee S, Shin M, Lee Y, Osmani L, Seong W, Cai H, Par-Young J, Ahn J, Park H, Kim M, Unlu S, Kim H, Han M, Dong X, You S, Lee E, Kang I. Investigating cytotoxic and inflammatory human IL-7 receptor low effector memory CD8+ T cells in lupus. EBioMedicine 2025, 119: 105898. PMID: 40857939, PMCID: PMC12398881, DOI: 10.1016/j.ebiom.2025.105898.Peer-Reviewed Original ResearchConceptsCD8<sup>+</sup> T cellsCD8<sup>+</sup> T cell subsetsT cell subsetsT cellsPeripheral bloodNeutrophil extracellular trapsEffector memoryGene signatureLupus pathogenesisImaging Mass CytometryEffector memory CD8+ T cellsCD8<sup>+</sup> T cell accumulationCD8<sup>+</sup> T cell infiltrationKidney tissueMemory CD8+ T cellsType I IFN gene signatureCD8+ T cellsEM CD8<sup>+</sup> T cellsAnalysis of immune cellsCytotoxic molecule expressionT cell infiltrationT cell accumulationAssociated with treatment outcomeKidney tissues of patientsT cell heterogeneityHeart of the matter: Neutrophils, cancer, and cardiovascular disease
Ambreen S, McCarthy A, Hidalgo A, Adrover J. Heart of the matter: Neutrophils, cancer, and cardiovascular disease. Journal Of Experimental Medicine 2025, 222: e20242402. PMID: 40788286, DOI: 10.1084/jem.20242402.Peer-Reviewed Original ResearchConceptsCardiovascular diseaseImmune cellsBurden of cardiovascular diseaseElevated burdenVascular endothelial cellsThrombotic eventsCardiovascular complicationsHypercoagulable stateTumor growthNeutrophil subtypesCancer patientsNeutrophil numbersVascular damageCancer progressionMyocardial infarctionCancerEndothelial cellsNeutrophilsDiseaseDisease statesPathological conditionsInflammationFrom complexity to consensus: A roadmap for neutrophil classification
Ng L, Ballesteros I, Cassatella M, Egeblad M, Fridlender Z, Gabrilovich D, Gao Q, Granot Z, Grieshaber-Bouyer R, Grimes H, Hedrick C, Hidalgo A, Kaplan M, Kubes P, Ling G, Lu L, Luo H, Mayadas T, Moutsopoulos N, Ng M, Nigrovic P, Ostuni R, Pittet M, Quail D, Silvestre-Roig C, Soehnlein O, Udalova I, Xue R, Zhang N, Kwok I. From complexity to consensus: A roadmap for neutrophil classification. Immunity 2025, 58: 1890-1903. PMID: 40763729, DOI: 10.1016/j.immuni.2025.07.011.Peer-Reviewed Original ResearchSecretory leukocyte protease inhibitor influences periarticular joint inflammation in Borrelia burgdorferi-infected mice
Yu Q, Tang X, Hart T, Homer R, Belperron A, Bockenstedt L, Ring A, Nakamura A, Fikrig E. Secretory leukocyte protease inhibitor influences periarticular joint inflammation in Borrelia burgdorferi-infected mice. ELife 2025, 14: rp104913. PMID: 40392222, PMCID: PMC12092001, DOI: 10.7554/elife.104913.Peer-Reviewed Original ResearchConceptsSecretory leukocyte protease inhibitorJoint inflammationC57BL/6 miceHigher infection loadTick-borne infectionsWild-type control miceClinical manifestations of infectionDevelopment of Lyme arthritisElevated serum levelsExcessive pro-inflammatory responsesManifestations of infectionProtease inhibitorsPro-inflammatory responseAnkle joint tissueInfection loadPromote tissue repairAnti-inflammatory effectsSerum levelsPeriarticular swellingClinical manifestationsControl miceTibiotarsal jointMMP-8Lyme diseaseIL-6A macrophage-neutrophil program drives mammary carcinogenesis
Bolini L, Knott S, Galluzzi L. A macrophage-neutrophil program drives mammary carcinogenesis. Trends In Cancer 2025, 11: 427-429. PMID: 40251071, DOI: 10.1016/j.trecan.2025.04.001.Peer-Reviewed Original ResearchMMP9High Neutrophils are Critical Mediators of Neutrophil Extracellular Traps Formation and Myocardial Ischemia/Reperfusion Injury
Hu S, Zhang F, Wang J, Zhang J, Li C, Lyu Y, Wang Y, Huang R, Gao Y, Yang H, Qian J, Tang W, Cao J, Ge J. MMP9High Neutrophils are Critical Mediators of Neutrophil Extracellular Traps Formation and Myocardial Ischemia/Reperfusion Injury. Advanced Science 2025, 12: 2415205. PMID: 40151877, PMCID: PMC12140383, DOI: 10.1002/advs.202415205.Peer-Reviewed Original ResearchConceptsNeutrophil extracellular trap formationNeutrophil extracellular trapsMyocardial ischemia/reperfusion injuryIschemia/reperfusion injuryBlood of healthy donorsNeutrophil-mediated reperfusion injuryTherapeutic targetExtracellular trap formationTranscription factor SPI1Potential therapeutic targetHealthy donorsIn vivo synergistic enhancement of MIF‐mediated inflammation in acute lung injury by the plant ortholog Arabidopsis MDL1
Spiller L, Zhang L, Gerra S, Stoppe C, Scheiermann P, Calandra T, Lolis E, Panstruga R, Bernhagen J, Hoffmann A. In vivo synergistic enhancement of MIF‐mediated inflammation in acute lung injury by the plant ortholog Arabidopsis MDL1. The FASEB Journal 2025, 39: e70489. PMID: 40134325, PMCID: PMC11937861, DOI: 10.1096/fj.202403301r.Peer-Reviewed Original ResearchConceptsAcute lung injuryLung injuryPulmonary infiltration of neutrophilsAdministered to C57BL/6 miceAcute respiratory distress syndromeParameters of lung injuryRespiratory distress syndromeInfiltration of neutrophilsPro-inflammatory cytokine genesPulmonary inflammationDistress syndromeC57BL/6 miceLeukocyte infiltrationArabidopsis thaliana proteinsInflammatory mediatorsHuman MIFMouse modelCytokine genesCombined treatmentFlow cytometryMonocytic cellsInflammationImmunofluorescence microscopyMIFInjuryNanoscopy reveals integrin clustering reliant on kindlin-3 but not talin-1
Wu Y, Cao Z, Liu W, Cahoon J, Wang K, Wang P, Hu L, Chen Y, Moser M, Vella A, Ley K, Wen L, Fan Z. Nanoscopy reveals integrin clustering reliant on kindlin-3 but not talin-1. Cell Communication And Signaling 2025, 23: 12. PMID: 39773732, PMCID: PMC11707915, DOI: 10.1186/s12964-024-02024-8.Peer-Reviewed Original ResearchTranscriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis
Divolis G, Synolaki E, Tringidou R, Tzouvelekis A, Boumpas D, Skendros P, Galani I. Transcriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis. Respiratory Research 2025, 26: 213. PMID: 40500689, PMCID: PMC12160113, DOI: 10.1186/s12931-025-03180-2.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosis patientsIdiopathic pulmonary fibrosisNeutrophil extracellular trapsPulmonary fibrosisIPF pathophysiologyPeripheral blood neutrophil countElevated peripheral blood neutrophil countsAcute respiratory distress syndromeCOVID-19 neutrophilsPeripheral blood of COVID-19 patientsLung biopsy specimensBlood of COVID-19 patientsRespiratory distress syndromeDeregulated immune responseNeutrophil extracellular trap formationBlood neutrophil countNeutrophil-driven pathologiesCOVID-19 pathogenesisCOVID-19 patientsLung biopsyBiopsy specimensDistress syndromePeripheral bloodNeutrophil countActivin/follistatin systemAdaptations of neutrophils in cancer
Ng M, Cerezo-Wallis D, Ng L, Hidalgo A. Adaptations of neutrophils in cancer. Immunity 2025, 58: 40-58. PMID: 39813993, DOI: 10.1016/j.immuni.2024.12.009.Peer-Reviewed Original Research
2024
Post‐exchange neutrophil count, but not post‐hematocrit, predicts endogenous erythropoiesis in patients with sickle cell disease undergoing chronic red cell exchange
Yurtsever N, Tong N, Geetha S, Nandi V, Shi P. Post‐exchange neutrophil count, but not post‐hematocrit, predicts endogenous erythropoiesis in patients with sickle cell disease undergoing chronic red cell exchange. Transfusion 2024, 64: 2270-2278. PMID: 39404130, DOI: 10.1111/trf.18044.Peer-Reviewed Original ResearchConceptsRed cell exchangeSickle cell diseaseChronic red cell exchangeCell exchangeSickle cell disease morbidityEndogenous erythropoiesisNeutrophil countCell diseaseAbsolute reticulocyte countPost-procedural parametersWhite cell countWhite blood cellsChronic transfusionPre-HCTSustained suppressionReticulocyte countRetrospective analysisWhite cell depletionMale genderCell depletionCell countIsovolemic hemodilutionReticulocytosisBlood cellsPatientsA nomogram combining neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) to predict distant metastasis in gastric cancer
Liu J, Sun R, Cai K, Xu Y, Yuan W. A nomogram combining neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) to predict distant metastasis in gastric cancer. Scientific Reports 2024, 14: 15391. PMID: 38965325, PMCID: PMC11224267, DOI: 10.1038/s41598-024-65307-7.Peer-Reviewed Original ResearchConceptsNeutrophil-to-lymphocyte ratioPrognostic nutritional indexPlatelet-to-lymphocyte ratioSystemic immune-inflammatory indexLymphocyte to monocyte ratioMultivariate logistic regression analysisDistant metastasisLogistic regression analysisLymphocyte ratioReceiver Operating CharacteristicGastric cancerValidation cohortPredictive factorsRisk factors of distant metastasisDistant metastasis of gastric cancerNutritional indexImmune-inflammatory indexClinical practiceNomogram's predictive performanceDecision curve analysisGastric cancer patientsMetastasis of gastric cancerEfficient nomogramRegression analysisMonocyte ratioNovel strategies for targeting neutrophil against myocardial infarction
Jiang K, Hwa J, Xiang Y. Novel strategies for targeting neutrophil against myocardial infarction. Pharmacological Research 2024, 205: 107256. PMID: 38866263, DOI: 10.1016/j.phrs.2024.107256.Peer-Reviewed Original ResearchThe brain structure, inflammatory, and genetic mechanisms mediate the association between physical frailty and depression
Jiang R, Noble S, Rosenblatt M, Dai W, Ye J, Liu S, Qi S, Calhoun V, Sui J, Scheinost D. The brain structure, inflammatory, and genetic mechanisms mediate the association between physical frailty and depression. Nature Communications 2024, 15: 4411. PMID: 38782943, PMCID: PMC11116547, DOI: 10.1038/s41467-024-48827-8.Peer-Reviewed Original ResearchConceptsIncident depressionPre-frailPhysical frailtyFrail individualsPopulation attributable fraction analysisRisk factors of depressionMendelian randomization analysisFactors of depressionPotential causal effectModifiable risk factorsNon-frail individualsCross-sectional studyEffect of frailtyHigher disease burdenUK BiobankRandomization analysisBrain volumeDepression casesDisease burdenFrailtyRegional brain volumesIncreased riskDepressionHigh riskFollow-upLipid mediators in neutrophil biology: inflammation, resolution and beyond
Ghodsi A, Hidalgo A, Libreros S. Lipid mediators in neutrophil biology: inflammation, resolution and beyond. Current Opinion In Hematology 2024, 31: 175-192. PMID: 38727155, PMCID: PMC11301784, DOI: 10.1097/moh.0000000000000822.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsAcute inflammationLipid mediatorsResolution of acute inflammationChronic inflammatory disordersExcessive neutrophil infiltrationCell surface G protein-coupled receptorsEndogenous lipid mediatorsTissue repair mechanismsResolution of inflammationPro-resolving mediatorsNeutrophil infiltrationChronic inflammationIschemic eventsInflammatory disordersInflammatory insultInflammation sitesInflammationNeutrophil phagocytosisCardiovascular diseaseNeutrophil functionNeutrophilsTherapeutic agentsNeutrophil heterogeneityNeutrophil apoptosisApoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages
Liebold I, Al Jawazneh A, Casar C, Lanzloth C, Leyk S, Hamley M, Wong M, Kylies D, Gräfe S, Edenhofer I, Aranda-Pardos I, Kriwet M, Haas H, Krause J, Hadjilaou A, Schromm A, Richardt U, Eggert P, Tappe D, Weidemann S, Ghosh S, Krebs C, A-Gonzalez N, Worthmann A, Lohse A, Huber S, Rothlin C, Puelles V, Jacobs T, Gagliani N, Bosurgi L. Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages. Science 2024, 384: eabo7027. PMID: 38574142, DOI: 10.1126/science.abo7027.Peer-Reviewed Original ResearchConceptsApoptotic neutrophilsApoptotic cellsIL-4-induced gene expressionUptake of apoptotic neutrophilsApoptotic cell clearanceCell lineage identityResponse to IL-4Cell identityEfferocytic macrophagesPhagocytic receptorsGene expressionLineage identityCell clearanceApoptotic hepatocytesHeterogeneous cellsCellsMouse modelT cellsParasite-induced pathologyIL-4HepatocytesMacrophagesInterleukin-4EngulfmentPhenotypeSmall-molecule CBP/p300 histone acetyltransferase inhibition mobilizes leukocytes from the bone marrow via the endocrine stress response
Jaschke N, Breining D, Hofmann M, Pählig S, Baschant U, Oertel R, Traikov S, Grinenko T, Saettini F, Biondi A, Stylianou M, Bringmann H, Zhang C, Yoshida T, Weidner H, Poller W, Swirski F, Göbel A, Hofbauer L, Rauner M, Scheiermann C, Wang A, Rachner T. Small-molecule CBP/p300 histone acetyltransferase inhibition mobilizes leukocytes from the bone marrow via the endocrine stress response. Immunity 2024, 57: 364-378.e9. PMID: 38301651, PMCID: PMC10923082, DOI: 10.1016/j.immuni.2024.01.005.Peer-Reviewed Original ResearchMeSH KeywordsBone MarrowHistone AcetyltransferasesHistonesHumansHypothalamo-Hypophyseal SystemNeutrophilsConceptsCorticotropin-releasing hormone receptor 1Hypothalamus-pituitary-adrenal glandAdrenocorticotropic hormoneBone marrowGranulocyte colony-stimulating factorAugmented host defenseMobilization of leukocytesColony-stimulating factorHistone acetyltransferase inhibitionHormone receptor 1Leukemic transformationG-CSFNeutrophil mobilizationReceptor 1Leukocyte mobilizationLeukocyte distributionHistone acetyltransferaseLeukocyte compartmentNeuroendocrine loopHost defenseEndocrine stress responseLeukocytesMarrowBloodReversible inhibitionNeutrophils in Physiology and Pathology
Aroca-Crevillén A, Vicanolo T, Ovadia S, Hidalgo A. Neutrophils in Physiology and Pathology. Annual Review Of Pathology Mechanisms Of Disease 2024, 19: 227-259. PMID: 38265879, PMCID: PMC11060889, DOI: 10.1146/annurev-pathmechdis-051222-015009.Peer-Reviewed Original ResearchMeSH KeywordsCardiovascular DiseasesCardiovascular InfectionsHealth PromotionHumansNeoplasmsNeutrophilsCell surface RNAs control neutrophil recruitment
Zhang N, Tang W, Torres L, Wang X, Ajaj Y, Zhu L, Luan Y, Zhou H, Wang Y, Zhang D, Kurbatov V, Khan S, Kumar P, Hidalgo A, Wu D, Lu J. Cell surface RNAs control neutrophil recruitment. Cell 2024, 187: 846-860.e17. PMID: 38262409, PMCID: PMC10922858, DOI: 10.1016/j.cell.2023.12.033.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEndothelial CellsMiceNeutrophil InfiltrationNeutrophilsNucleotide Transport ProteinsRNAConceptsCell surfaceMammalian homologOuter cell surfaceRNA transportGlycan modificationsMammalian cellsSID-1Cellular functionsRecruitment to inflammatory sitesGlycoRNARNAMurine neutrophilsFunctional significanceNeutrophil recruitmentNeutrophil recruitment to inflammatory sitesBiological importanceCellsNeutrophil adhesionReduced neutrophil adhesionHomologyGlycansGenesInflammatory sitesRecruitmentEndothelial cells
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