2025
ENaC contributes to macrophage dysfunction in cystic fibrosis
Moran J, Pugh C, Brown N, Thomas A, Zhang S, McCauley E, Cephas A, Shrestha C, Partida-Sanchez S, Bai S, Bruscia E, Kopp B. ENaC contributes to macrophage dysfunction in cystic fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2025, 329: l61-l69. PMID: 40454714, PMCID: PMC12181047, DOI: 10.1152/ajplung.00009.2025.Peer-Reviewed Original ResearchConceptsCystic fibrosis transmembrane conductance regulatorCystic fibrosis transmembrane conductance regulator modulatorsMonocyte-derived macrophagesEpithelial sodium channelTransmembrane conductance regulatorCystic fibrosisImmune cellsProinflammatory cytokine productionENaC modulationENaC expressionConductance regulatorCystic fibrosis transmembrane conductance regulator inhibitionCytokine productionSodium channelsCF airway epithelial cellsReduced proinflammatory cytokine productionDecreased proinflammatory cytokine productionSodium channel expressionInfection controlTherapeutic targetAirway epithelial cellsIon channel dysfunctionReactive oxygen speciesIon channelsCFTR expressionExtracellular Vesicle (EV) Targeted Cells Release Secondary Effector EVs: Indication of How To Account for Histocompatibility and Disease Specificity of EV Treatments
Askenase P. Extracellular Vesicle (EV) Targeted Cells Release Secondary Effector EVs: Indication of How To Account for Histocompatibility and Disease Specificity of EV Treatments. Journal Of Extracellular Vesicles 2025, 14: e70076. PMID: 40415199, PMCID: PMC12104073, DOI: 10.1002/jev2.70076.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsExtracellular VesiclesHumansMacrophagesMesenchymal Stem CellsSpinal Cord InjuriesConceptsMesenchymal stromal cellsSpinal cord injuryT cellsExtracellular vesiclesEffector T cellsSuppressor T cellsDisease specificityTreating spinal cord injuryImmune toleranceHistocompatibility barriersRecipient macrophagesEV treatmentStromal cellsTarget cellsCord injuryMSC-derivedPathological conditionsDiverse injuriesCellsInjuryDiseasePer treatmentTreatmentHealingHealing effectSecretory 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-6Outer membrane tube formation by Francisella novicida involves extensive envelope modifications and is linked with type VI secretion and alterations to the host phagosomal membrane
Rashid M, Tachiyama S, Zhu S, Zhao H, McCaig W, Sun J, Li H, Liu J, Thanassi D. Outer membrane tube formation by Francisella novicida involves extensive envelope modifications and is linked with type VI secretion and alterations to the host phagosomal membrane. MBio 2025, 16: e01060-25. PMID: 40387340, PMCID: PMC12153307, DOI: 10.1128/mbio.01060-25.Peer-Reviewed Original ResearchConceptsType VI secretion systemOuter membrane vesiclesVI secretion systemZoonotic disease tularemiaPhagosomal escapePhagosomal membraneSecretion systemMembrane tubulesMacrophage phagosomesDisease tularemiaCryogenic electron tomographyResponse to amino acid starvationTubular extensionsCellular transformationSpherical outer membrane vesiclesType VI secretionAmino acid starvationCell surfaceDynamic cytoplasmic organellesHost-pathogen interactionsDynamic cytoplasmic structuresIntracellular bacterial pathogensCo-localizationResponse to specific cuesTube formationCardiac macrophage: Insights from murine models to translational potential for human studies
Liu Y, Wang T, Lu Y, Riaz M, Qyang Y. Cardiac macrophage: Insights from murine models to translational potential for human studies. Journal Of Molecular And Cellular Cardiology 2025, 204: 17-31. PMID: 40354877, PMCID: PMC12162190, DOI: 10.1016/j.yjmcc.2025.05.001.Peer-Reviewed Original ResearchConceptsCardiovascular diseaseMurine studiesCardiac macrophagesImmune cellsDisease progressionCardiac homeostasisHuman studiesFunctional significanceCell typesTherapeutic targetCardiac microenvironmentTranslational potentialProgressive pathologyDevelopmental originsPhysiological maintenanceMacrophagesMicroenvironmentMechanical stimuliDiseaseFunctional responseCellsDynamic roleExperimental toolHuman modelLineagesYou know my NAMs
Ghosh S, Rothlin C. You know my NAMs. Immunity 2025, 58: 1179-1181. PMID: 40367920, DOI: 10.1016/j.immuni.2025.04.025.Peer-Reviewed Original ResearchUnveiling fine-scale spatial structures and amplifying gene expression signals in ultra-large ST slices with HERGAST
Gong Y, Yuan X, Jiao Q, Yu Z. Unveiling fine-scale spatial structures and amplifying gene expression signals in ultra-large ST slices with HERGAST. Nature Communications 2025, 16: 3977. PMID: 40295488, PMCID: PMC12037780, DOI: 10.1038/s41467-025-59139-w.Peer-Reviewed Original ResearchConceptsGene expression signalsSpatial transcriptomics data analysisExpression signalsTranscriptome data analysisHeterogeneous graph networkReal-world datasetsSpatial expression patternsOver-smoothing problemSpatial transcriptomics dataGlobal spatial relationshipsST data analysisTranscriptome dataUltra-large-scaleConquer strategyExpression patternsGraph networkData splittingGenesStructural and functional significance of Aedes aegypti AgBR1 flavivirus immunomodulator
Martinez-Castillo A, Barriales D, Azkargorta M, Zalamea J, Ardá A, Jimenez-Barbero J, Gonzalez-Lopez M, Aransay A, Marín-López A, Fikrig E, Elortza F, Anguita J, Abrescia N. Structural and functional significance of Aedes aegypti AgBR1 flavivirus immunomodulator. Journal Of Virology 2025, 99: e01878-24. PMID: 40272158, PMCID: PMC12090808, DOI: 10.1128/jvi.01878-24.Peer-Reviewed Original ResearchConceptsSalivary gland proteinsGland proteinsMosquito-borne virusesFunctional significanceHost-cell responsesMosquito salivary gland proteinsProtein functionMosquito proteinsFunctional insightsThree-dimensional structureMurine primary macrophagesZika virusA-resolutionEnzymatic activityInfluence virus transmissionProteinBlood feedingCross-talkVirus entrySpread of mosquito-borne diseasesPrimary macrophagesCell proliferationInteraction studiesViral replicationPrevent Zika virusSustained tenascin-C expression drives neointimal hyperplasia and promotes aortocaval fistula failure
Gonzalez L, Zhang W, Bai H, Taniguchi R, Ramachandra A, Jovin D, Ohashi Y, Nguyen M, Thaxton C, Yatsula B, Vazquez-Padron R, Humphrey J, Martin K, Kyriakides T, Dardik A. Sustained tenascin-C expression drives neointimal hyperplasia and promotes aortocaval fistula failure. AJP Heart And Circulatory Physiology 2025, 328: h1147-h1167. PMID: 40247455, PMCID: PMC12150301, DOI: 10.1152/ajpheart.00661.2024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArteriovenous Shunt, SurgicalDisease Models, AnimalGraft Occlusion, VascularHuman Umbilical Vein Endothelial CellsHumansHyperplasiaMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutMyocytes, Smooth MuscleNeointimaNF-kappa BTenascinThrombomodulinVascular PatencyVascular RemodelingVena Cava, InferiorConceptsArteriovenous fistula patencyTenascin-C expressionArteriovenous fistulaTissue factor expressionEnd-stage kidney diseaseAnti-inflammatory macrophage polarizationNeointimal hyperplasiaWT miceTenascin-CInflammatory microenvironmentWild-typeFactor expressionMacrophage polarizationArteriovenous fistula outcomesArteriovenous fistula failurePatent arteriovenous fistulaVein smooth muscle cellsArteriovenous fistula maturationSmooth muscle cellsOccluded arteriovenous fistulaHuman umbilical vein smooth muscle cellsImprove dialysis outcomesHuman umbilical vein endothelial cellsRegulation of inflammationNF-kB activationA 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 ResearchActivation of macrophages by extracellular vesicles derived from Babesia-infected red blood cells
Hagos B, Brasov I, Branscome H, Rashid S, Bradford R, Leonelli J, Kashanchi F, Mamoun C, Molestina R. Activation of macrophages by extracellular vesicles derived from Babesia-infected red blood cells. Infection And Immunity 2025, 93: e00333-24. PMID: 40172538, PMCID: PMC12070731, DOI: 10.1128/iai.00333-24.Peer-Reviewed Original ResearchConceptsInfected red blood cellsPrimary cause of human babesiosisRed blood cellsExtracellular vesiclesActivated macrophagesResponse to <i>B.Host-pathogen interactionsModulation of pro-inflammatory cytokinesBlood cellsElimination of parasitesPro-inflammatory cytokinesActivation of NF-kBActivation of macrophagesRelease of extracellular vesiclesInnate immune responseIncubation of macrophagesUninfected RBCsCo-culture experimentsHuman babesiosisProtozoan parasitesCytokine secretionImmune responseMacrophage activationBabesiosisEV fractionsSrsf3-Dependent APA Drives Macrophage Maturation and Limits Atherosclerosis
Yang X, Zhang X, Tian Y, Yang J, Jia Y, Xie Y, Cheng L, Chen S, Wu L, Qin Y, Zhao Z, Zhao D, Wei Y. Srsf3-Dependent APA Drives Macrophage Maturation and Limits Atherosclerosis. Circulation Research 2025, 136: 985-1009. PMID: 40160097, DOI: 10.1161/circresaha.124.326111.Peer-Reviewed Original ResearchConceptsAlternative polyadenylationAssociated with atherosclerosis progressionUntranslated regionRNA sequencingExpression of chemokinesRegulation of cell fateAlternative polyadenylation patternsEfficient mitochondrial translationMetabolic labeling assaysSingle-cell RNA sequencingIntegrated stress responseMyeloid deletionLow-density lipoproteinMonocytes to macrophagesImpairment of protein synthesisPhagocytic impairmentMetabolomic profilesMacrophage maturationPrecursor nicotinamide mononucleotideCirculating monocytesIntegrated stress response inhibitorLesional cellsHistopathological analysisProatherosclerotic effectsNicotinamide mononucleotide treatmentSIMVI disentangles intrinsic and spatial-induced cellular states in spatial omics data
Dong M, Su D, Kluger H, Fan R, Kluger Y. SIMVI disentangles intrinsic and spatial-induced cellular states in spatial omics data. Nature Communications 2025, 16: 2990. PMID: 40148341, PMCID: PMC11950362, DOI: 10.1038/s41467-025-58089-7.Peer-Reviewed Original ResearchConceptsOmics dataSpatial omics dataAnalysis of gene expressionSingle-cell resolutionDownstream analysisCellular statesSpatial interaction modelsGerminal center B cellsGene expressionCommunication machineryOmics technologiesIntercellular interactionsSpatial omics technologiesTumor microenvironmentB cellsSpatial dynamicsHuman tonsilsMacrophage stateSpatial effectsCytoplasmic Mg2+ supersedes carbon source preference to dictate Salmonella metabolism
Pokorzynski N, Jones K, Campagna S, Groisman E. Cytoplasmic Mg2+ supersedes carbon source preference to dictate Salmonella metabolism. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2424337122. PMID: 40131949, PMCID: PMC12002343, DOI: 10.1073/pnas.2424337122.Peer-Reviewed Original ResearchConceptsCAMP receptor proteinCarbon source preferenceUptake genesCarbon sourceCyclic adenosine monophosphateCyclic adenosine monophosphate receptor proteinCytoplasmic MgCarbon source uptakeSynthesis of cyclic adenosine monophosphateSalmonella metabolismUtilization genesCRP-cAMPCarbon utilizationMaster regulatorsAllosteric activationDecreased transcriptionIncreased transcriptionGenesTranscriptionMetabolic restrictionsReceptor proteinTyphimuriumCyclic adenosine monophosphate concentrationsMurine macrophagesReduced synthesisTranscriptomic profiling after B-cell depletion reveals central and peripheral immune cell changes in multiple sclerosis
Wei J, Moon J, Yasumizu Y, Zhang L, Raddassi K, Buitrago-Pocasangre N, Deerhake M, Strauli N, Chen C, Herman A, Pedotti R, Raposo C, Yim I, Pappalardo J, Longbrake E, Sumida T, Axisa P, Hafler D. Transcriptomic profiling after B-cell depletion reveals central and peripheral immune cell changes in multiple sclerosis. Journal Of Clinical Investigation 2025, 135: e182790. PMID: 40067358, PMCID: PMC12126227, DOI: 10.1172/jci182790.Peer-Reviewed Original ResearchConceptsB-cell depletionImmune landscapeMultiple sclerosisAnti-CD20-mediated B-cell depletionPeripheral CD4+ T cell populationsEffect of B cell depletionB cell depletion treatmentCD4+ T cell populationB cell depletion therapyCerebrospinal fluidCD4+ T cellsTreatment of early diseaseCD16+ monocytesImmune cell changesImmune cell subsetsT cell populationsPeripheral blood monocytesFlow cytometry-based methodTNF-a mRNACell type-specific changesCell subsetsT cellsImmunological changesAutoimmune activityB cellsAn antibody–toxin conjugate targeting CD47 linked to the bacterial toxin listeriolysin O for cancer immunotherapy
Schrank B, Wang Y, Wu A, Tran N, Lee D, Edwards J, Huntoon K, Dong S, Ha J, Ma Y, Grippin A, Jeong S, Antony A, Chang M, Kang M, Gallup T, Koong A, Li J, Yun K, Kim B, Jiang W. An antibody–toxin conjugate targeting CD47 linked to the bacterial toxin listeriolysin O for cancer immunotherapy. Nature Cancer 2025, 6: 511-527. PMID: 40000910, PMCID: PMC11952976, DOI: 10.1038/s43018-025-00919-0.Peer-Reviewed Original ResearchConceptsAntibody-toxin conjugatesTumor cellsImmune recognition of tumor cellsEnhanced antigen cross-presentationRecognition of tumor cellsCancer cell phagocytosisTumor-derived antigensToxin listeriolysin OTumor-derived peptidesImproved animal survivalPromote immune recognitionCytosolic immune sensorsIntracellular bacterium Listeria monocytogenesTreatment in vivoTreating multiple cancersPhagocytosis checkpointsCheckpoint blockadeCancer immunotherapySignal CD47Listeriolysin OMetastatic breastMelanoma tumorsTherapeutic strategiesAnimal survivalCell phagocytosisCold and hot fibrosis define clinically distinct cardiac pathologies
Miyara S, Adler M, Umansky K, Häußler D, Bassat E, Divinsky Y, Elkahal J, Kain D, Lendengolts D, Flores R, Bueno-Levy H, Golani O, Shalit T, Gershovits M, Weizman E, Genzelinakh A, Kimchi D, Shakked A, Zhang L, Wang J, Baehr A, Petrover Z, Sarig R, Dorn T, Moretti A, Saez-Rodriguez J, Kupatt C, Tanaka E, Medzhitov R, Krüger A, Mayo A, Alon U, Tzahor E. Cold and hot fibrosis define clinically distinct cardiac pathologies. Cell Systems 2025, 16: 101198. PMID: 39970910, PMCID: PMC11922821, DOI: 10.1016/j.cels.2025.101198.Peer-Reviewed Original ResearchConceptsHeart failureMyocardial infarctionAutocrine growth factor loopsUnmet medical needCardiac fibrosisNeutralizing antibodiesReduced fibrosisTreatment strategiesMyofibroblast proliferationAcute MIFibrosis post-MICardiac pathologyFibrosisTherapeutic approachesPost-MIChronic injuryMyofibroblastsMedical needFactor loopsMulti-Scale Multi-Cell Computational Model of Inflammation-Mediated Aortic Remodeling in Hypertension
Estrada A, Humphrey J. Multi-Scale Multi-Cell Computational Model of Inflammation-Mediated Aortic Remodeling in Hypertension. Annals Of Biomedical Engineering 2025, 53: 1014-1023. PMID: 39904866, PMCID: PMC12067544, DOI: 10.1007/s10439-025-03685-3.Peer-Reviewed Original ResearchDeletion of sphingosine 1-phosphate receptor 1 in myeloid cells reduces hepatic inflammatory macrophages and attenuates MASH
Parthasarathy G, Venkatesan N, Sidhu G, Song M, Liao C, Barrow F, Mauer A, Sehrawat T, Nakao Y, Daniel P, Dasgupta D, Pavelko K, Revelo X, Malhi H. Deletion of sphingosine 1-phosphate receptor 1 in myeloid cells reduces hepatic inflammatory macrophages and attenuates MASH. Hepatology Communications 2025, 9: e0613. PMID: 39899672, DOI: 10.1097/hc9.0000000000000613.Peer-Reviewed Original ResearchConceptsMyeloid cellsMonocyte-derived macrophagesHigh-fatLiver injuryProinflammatory monocyte-derived macrophagesReceptor 1Cell-specific knockout miceMass cytometryT cell subsetsSphingosine 1-phosphate receptor 1Cardiometabolic risk factorsS1P receptor 1Accumulation of monocyte-derived macrophagesImmune cell typesWild-typeLiver inflammatory infiltrationGene ontology pathway analysisWild-type controlsDevelopment of steatohepatitisSphingosine 1-phosphateMitogen-activated protein kinase pathwayT cellsIntrahepatic macrophagesInflammatory infiltrateKnockout mice
2024
Malate initiates a proton-sensing pathway essential for pH regulation of inflammation
Chen Y, Shi R, Xiang Y, Fan L, Tang H, He G, Zhou M, Feng X, Tan J, Huang P, Ye X, Zhao K, Fu W, Li L, Bian X, Chen H, Wang F, Wang T, Zhang C, Zhou B, Chen W, Liang T, Lv J, Kang X, Shi Y, Kim E, Qin Y, Hettinghouse A, Wang K, Zhao X, Yang M, Tang Y, Piao H, Guo L, Liu C, Miao H, Tang K. Malate initiates a proton-sensing pathway essential for pH regulation of inflammation. Signal Transduction And Targeted Therapy 2024, 9: 367. PMID: 39737965, PMCID: PMC11683149, DOI: 10.1038/s41392-024-02076-9.Peer-Reviewed Original ResearchConceptsL-malateInflammatory responseCytosolic pHBind BiPTCA intermediatesSensing pathwaysRegulation of inflammatory responsesBiological informationAnti-inflammatory metabolitesAnti-inflammatory proteinPro-inflammatory macrophagesRegulation of inflammationSignaling modalitiesPhysiological adaptationsAnti-inflammatory effectsIRF2BP2BiPPH regulationCarboxylate metaboliteChemical languageIn vivoIn vitroMacrophagesPathwayPH reduction
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