2025
Plasma CHI3L1 associates with brain volume loss and glial activation in multiple sclerosis
Ahola V, Saraste M, Nylund M, Matilainen M, Luoma A, Vuorimaa A, Lehto J, Laaksonen S, Brockmann E, Kuhle J, Leppert D, Soukka T, Lamminmäki U, Airas L. Plasma CHI3L1 associates with brain volume loss and glial activation in multiple sclerosis. Journal Of Neurology Neurosurgery & Psychiatry 2025, jnnp-2025-336063. PMID: 40379482, DOI: 10.1136/jnnp-2025-336063.Peer-Reviewed Original ResearchDistribution volume ratioBrain volume lossHealthy controlsPositron emission tomographyPlasma CHI3L1Smoldering inflammationMultiple sclerosisGlial activationInnate immune cell activationAssociated with Expanded Disability Status ScaleImmune cell activationChitinase-3-like protein 1Expanded Disability Status ScaleAssociated with smaller brain volumesDisability Status ScaleCHI3L1 concentrationsIndependent of relapsesVolume lossStudy cohortCell activationImaging outcomesTSPO-PETCHI3L1Emission tomographyStatus ScaleCCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models
Leser F, Júnyor F, Pagnoncelli I, Delgado A, Medeiros I, Nóbrega A, Andrade B, de Lima M, da Silva N, Jacob L, Boyé K, Geraldo L, de Souza A, Maron-Gutierrez T, Castro-Faria-Neto H, Follmer C, Braga C, Neves G, Eichmann A, Romão L, Lima F. CCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models. Journal Of Neuroinflammation 2025, 22: 31. PMID: 39894839, PMCID: PMC11789347, DOI: 10.1186/s12974-024-03318-x.Peer-Reviewed Original ResearchConceptsMouse model of PDModel of PDMouse modelDopaminergic neuronsNeuron-microglia communicationNeuron-glia communicationParkinson's diseaseCCR7-dependent mannerMicroglial cell activationCCR7 expressionCCL21-CCR7Progressive degenerative diseaseCCR7 receptorMicroglial cell migrationInflammatory profileChemokine CCL21Cell activationCCL21Therapeutic strategiesChemokine inhibitorsTherapeutic implicationsMicroglial activationReceptor pathwayCCR7Behavioral deficits
2024
A safe insect-based chikungunya fever vaccine affords rapid and durable protection in cynomolgus macaques
Adam A, Woolsey C, Lu H, Plante K, Wallace S, Rodriguez L, Shinde D, Cui Y, Franz A, Thangamani S, Comer J, Weaver S, Wang T. A safe insect-based chikungunya fever vaccine affords rapid and durable protection in cynomolgus macaques. Npj Vaccines 2024, 9: 251. PMID: 39702442, PMCID: PMC11659317, DOI: 10.1038/s41541-024-01047-z.Peer-Reviewed Original ResearchMemory B cellsCynomolgus macaquesB cellsDose vaccinationAntigen presenting cell activationReceptor signalingCHIK feverNK cell responsesRobust type I interferonT cell responsesT cell immunityMultiple innate immune pathwaysToll-like receptor signalingWild-typeDose-dependent mannerSkin hypersensitivity reactionsType I interferonInnate immune signalingInnate immune pathwaysT cellsMechanisms of host protectionCHIKV infectionCell activationHypersensitivity reactionsAntibody responseCasRx-based Wnt activation promotes alveolar regeneration while ameliorating pulmonary fibrosis in a mouse model of lung injury
Shen S, Wang P, Wu P, Huang P, Chi T, Xu W, Xi Y. CasRx-based Wnt activation promotes alveolar regeneration while ameliorating pulmonary fibrosis in a mouse model of lung injury. Molecular Therapy 2024, 32: 3974-3989. PMID: 39245939, PMCID: PMC11573616, DOI: 10.1016/j.ymthe.2024.09.008.Peer-Reviewed Original ResearchWnt/b-catenin signalingStem cell activityLung epitheliumAlveolar regenerationPulmonary fibrosisLung fibrosisWnt signalingCell activationMouse models of lung injuryModel of lung injuryWnt activityAlveolar type II cell proliferationBleomycin-induced injuryAmeliorated pulmonary fibrosisActivation of Wnt signalingType II cell proliferationInhibit lung fibrosisRegenerative medicineAnti-fibrotic effectsTreating pulmonary fibrosisActivated Wnt signalingLung injuryMouse modelFibrosisWnt/b-cateninMeningeal lymphatic function promotes oligodendrocyte survival and brain myelination
das Neves S, Delivanoglou N, Ren Y, Cucuzza C, Makuch M, Almeida F, Sanchez G, Barber M, Rego S, Schrader R, Faroqi A, Thomas J, McLean P, Oliveira T, Irani S, Piehl F, Da Mesquita S. Meningeal lymphatic function promotes oligodendrocyte survival and brain myelination. Immunity 2024, 57: 2328-2343.e8. PMID: 39217987, PMCID: PMC11464205, DOI: 10.1016/j.immuni.2024.08.004.Peer-Reviewed Original ResearchLymphatic functionMeningeal lymphatic dysfunctionLymphatic dysfunctionVascular endothelial growth factor-CState of immunosuppressionMyeloid cell activationHuman demyelinating diseasesBrain myelinMature oligodendrocyte numbersClinical relapseImmunocompetent miceAdult miceMeningeal lymphatic functionAxonal lossOligodendrocyte survivalDemyelinating diseaseOligodendrocyte numbersVessel ablationAdaptive immunityCell activationCerebrospinal fluidGene expression changesMature oligodendrocytesOligodendrocyte functionGlial cellsCarbon monoxide-loaded red blood cells ameliorate metabolic dysfunction-associated steatohepatitis progression via enhancing AMP-activated protein kinase activity and inhibiting Kupffer cell activation
Yanagisawa H, Maeda H, Noguchi I, Tanaka M, Wada N, Nagasaki T, Kobayashi K, Kanazawa G, Taguchi K, Chuang V, Sakai H, Nakashima H, Kinoshita M, Kitagishi H, Iwakiri Y, Sasaki Y, Tanaka Y, Otagiri M, Watanabe H, Maruyama T. Carbon monoxide-loaded red blood cells ameliorate metabolic dysfunction-associated steatohepatitis progression via enhancing AMP-activated protein kinase activity and inhibiting Kupffer cell activation. Redox Biology 2024, 76: 103314. PMID: 39163766, PMCID: PMC11381851, DOI: 10.1016/j.redox.2024.103314.Peer-Reviewed Original ResearchAMP-activated protein kinaseKupffer cell activationHeme oxygenase-1Red blood cellsInhibit Kupffer cell activationLiver heme oxygenase-1Suppress Kupffer cell activationCell activationLiver regenerationModel miceBlood cellsFat accumulationActivating AMP-activated protein kinaseAMP-activated protein kinase activationImpaired liver regenerationMethionine-choline deficient dietNonalcoholic fatty liver diseaseRestore liver regenerationFatty liver diseaseReceptor inductionHealthy miceProtein kinase activityPromoting fatty acid oxidationMouse modelLiver diseaseLupus Nephritis: Immune Cells and the Kidney Microenvironment
Chernova I. Lupus Nephritis: Immune Cells and the Kidney Microenvironment. Kidney360 2024, 5: 1394-1401. PMID: 39120952, PMCID: PMC11441818, DOI: 10.34067/kid.0000000000000531.Peer-Reviewed Original ResearchIntrinsic renal cellsLupus nephritisImmune cellsRenal cellsProgression to end-stage kidney diseaseActivation of immune cellsProinflammatory cytokine milieuSystemic immunosuppressive effectsAutoimmune disease systemic lupus erythematosusDisease systemic lupus erythematosusImmune cell activationSystemic lupus erythematosusEnd-stage kidney diseaseLN therapyCytokine milieuKidney cell functionImmune infiltrationKidney microenvironmentOrgan manifestationsLupus erythematosusAntigen presentationCytokine productionImmunosuppressive effectsKidney diseaseCell activationA Pilot Study on the Proteomics Profile of Serum Exosome-Enriched Extracellular Vesicles from Normal versus Individuals with Obesity-Related Insulin Resistance
Saraswathi V, Ai W, Kumar V, Sharma K, Gopal T, Kumar N, Malhi H, Sehrawat T, Desouza C. A Pilot Study on the Proteomics Profile of Serum Exosome-Enriched Extracellular Vesicles from Normal versus Individuals with Obesity-Related Insulin Resistance. Biomedicines 2024, 12: 799. PMID: 38672154, PMCID: PMC11048419, DOI: 10.3390/biomedicines12040799.Peer-Reviewed Original ResearchObesity-related insulin resistanceIngenuity Pathway AnalysisInsulin resistanceB cellsRegulate immune cell activationSerum exosomesImmune cell activationIsolated serum exosomesB cell activationRisk of diabetesHigh-risk individualsExosome-enriched extracellular vesiclesProteomic profilingProgression of diabetesIngenuity Pathway Analysis analysesCell activationInsulin sensitivityProtein expressionOB-IRExosomal proteinsTherapeutic targetMale subjectsExtracellular vesiclesExtracellular spaceInflammationNeurosyphilis is characterized by a compartmentalized and robust neuroimmune response but not by neuronal injury
Catalano A, Yoon J, Fertuzinhos S, Reisert H, Walsh H, Kosana P, Wilson M, Gisslen M, Zetterberg H, Marra C, Farhadian S. Neurosyphilis is characterized by a compartmentalized and robust neuroimmune response but not by neuronal injury. Med 2024, 5: 321-334.e3. PMID: 38513660, PMCID: PMC11216317, DOI: 10.1016/j.medj.2024.02.005.Peer-Reviewed Original ResearchMarker of neuronal injuryNeuronal injuryNeurological symptomsWhite blood cell count <Immune responsePresence of neurological symptomsNeuroinflammatory diseasesCell count <CSF-VDRL testPlasma reagin titerCNS immune responsesCNS-specific immune responseImmune cell activationCSF inflammatory responseCSF cellsNeurosyphilis casesAsymptomatic neurosyphilisCSF neopterinImmune profileNeuroimmune responseHIV statusNational Institutes of HealthNeurosyphilisCell activationInflammatory responseWnt5 controls splenic myelopoiesis and neutrophil functional ambivalency during DSS-induced colitis
Luan Y, Hu J, Wang Q, Wang X, Li W, Qu R, Yang C, Rajendran B, Zhou H, Liu P, Zhang N, Shi Y, Liu Y, Tang W, Lu J, Wu D. Wnt5 controls splenic myelopoiesis and neutrophil functional ambivalency during DSS-induced colitis. Cell Reports 2024, 43: 113934. PMID: 38461416, PMCID: PMC11064424, DOI: 10.1016/j.celrep.2024.113934.Peer-Reviewed Original ResearchCD8<sup>+</sup> T cell activationNeutrophil productionNeutrophil plasticitySplenic extramedullary myelopoiesisFamily member 5T cell activationInnate immune cellsSplenic stromal cellsDSS-induced colitisAnti-inflammatory protectionCD101 expressionPro-inflammatory activitySplenic myelopoiesisExtramedullary myelopoiesisBone marrowImmune cellsSplenic neutrophilsMember 5Autoimmune diseasesInflammatory outcomesCell activationStromal cellsColitisSplenic productionElevated numbersNew approaches for understanding the potential role of microbes in Alzheimer's disease
Whitson H, Banks W, Diaz M, Frost B, Kellis M, Lathe R, Schmader K, Spudich S, Tanzi R, Garden G. New approaches for understanding the potential role of microbes in Alzheimer's disease. Brain Behavior & Immunity - Health 2024, 36: 100743. PMID: 38435720, PMCID: PMC10906156, DOI: 10.1016/j.bbih.2024.100743.Peer-Reviewed Original ResearchAlzheimer's diseaseAD pathologyAntimicrobial protection hypothesisInfluence AD pathologyGene-environment interactionsModel organismsMicrobial organismsMicrobesPotential roleAmyloid accumulationProtection hypothesisAlzheimerImmune cell activationReview new evidencePathological processesCell activationComplex pathological processAmyloidGermOrganizationAlzheimer's Disease Research CenterStem cell migration drives lung repair in living mice
Chioccioli M, Liu S, Magruder S, Tata A, Borriello L, McDonough J, Konkimalla A, Kim S, Nouws J, Gonzalez D, Traub B, Ye X, Yang T, Entenberg D, Krishnaswamy S, Hendry C, Kaminski N, Tata P, Sauler M. Stem cell migration drives lung repair in living mice. Developmental Cell 2024, 59: 830-840.e4. PMID: 38377991, PMCID: PMC11003834, DOI: 10.1016/j.devcel.2024.02.003.Peer-Reviewed Original ResearchStem cell migrationCell migrationAlveolar type 2 cellsAlveolar unitsStem cell motilityAlveolar type 1 cellsStem cell activityCellular response to injuryResponse to injuryType 2 cellsMotile phenotypeType 1 cellsCell motilityLung repairImpaired regenerationGenetic depletionCell activationAT2Stem cellsTissue repairAT1Longitudinal imagingInjuryMotilityCellular resolutionSpatial Transcriptomics Resolve an Emphysema-Specific Lymphoid Follicle B Cell Signature in Chronic Obstructive Pulmonary Disease
Rojas-Quintero J, Ochsner S, New F, Divakar P, Yang C, Wu T, Robinson J, Chandrashekar D, Banovich N, Rosas I, Sauler M, Kheradmand F, Gaggar A, Margaroli C, San Jose Estepar R, McKenna N, Polverino F. Spatial Transcriptomics Resolve an Emphysema-Specific Lymphoid Follicle B Cell Signature in Chronic Obstructive Pulmonary Disease. American Journal Of Respiratory And Critical Care Medicine 2024, 209: 48-58. PMID: 37934672, PMCID: PMC10870877, DOI: 10.1164/rccm.202303-0507le.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseB cell activationObstructive pulmonary diseaseLymphoid folliclesCell activationPulmonary diseaseGOLD 1Chronic Obstructive Lung Disease (GOLD) 1Chronic B-cell activationB cell signaturesDegree of emphysemaB cell marker genesB cell maturationSevere emphysemaAntiinflammatory profileEmphysema measurementsTomographic scanLung sectionsAntigen presentationGOLD 3Centrilobular emphysemaImmune componentsEmphysema pathogenesisEmphysemaLung samples
2023
Metabolic fitness of IgA+ plasma cells in the gut requires DOCK8
Zhang B, Chen S, Yin X, McBride C, Gertie J, Yurieva M, Bielecka A, Hoffmann B, Hinson J, Grassmann J, Xu L, Siniscalco E, Soldatenko A, Hoyt L, Joseph J, Norton E, Uthaman G, Palm N, Liu E, Eisenbarth S, Williams A. Metabolic fitness of IgA+ plasma cells in the gut requires DOCK8. Mucosal Immunology 2023, 17: 431-449. PMID: 38159726, PMCID: PMC11571232, DOI: 10.1016/j.mucimm.2023.12.001.Peer-Reviewed Original ResearchPlasma cellsLamina propriaT cell-dependent antigensCytokinesis 8 (DOCK8) mutationsDOCK8-deficient miceMucosal IgA productionRecurrent gastrointestinal infectionGut lamina propriaPoor antibody responseIgA class switchingAntigen-specific IgAEarly B cell activationLong-term survivalB cell activationGut IgAFood antigensAntibody responseIgA productionImmune homeostasisGastrointestinal infectionsPrimary immunodeficiencyT cellsPC compartmentB cellsCell activationSpatial Transcriptomics Resolve an Emphysema-specific Lymphoid Follicle B Cell Signature in COPD.
Rojas-Quintero J, Ochsner S, New F, Divakar P, Yang C, Wu T, Robinson J, Shimoga Chandrashekar D, Banovich N, Rosas I, Sauler M, Kheradmand F, Gaggar A, Margaroli C, San Jose Estepar R, McKenna N, Polverino F. Spatial Transcriptomics Resolve an Emphysema-specific Lymphoid Follicle B Cell Signature in COPD. American Journal Of Respiratory And Critical Care Medicine 2023 PMID: 38064378, DOI: 10.1164/rccm.202303-0507oc.Peer-Reviewed Original ResearchChronic obstructive pulmonary diseaseB cell activationLymphoid folliclesCOPD patientsGOLD 1Cell activationChronic B-cell activationObstructive pulmonary diseaseB cell signaturesAnti-inflammatory profileChest CT scanDegree of emphysemaB cell marker genesB cell maturationSevere emphysemaPulmonary diseaseEmphysema measurementsLung sectionsAntigen presentationGOLD 3Centrilobular emphysemaCT scanImmune componentsEmphysema pathogenesisEmphysemaClonally expanded memory CD8+ T cells accumulate in atherosclerotic plaques and are pro-atherogenic in aged mice
Tyrrell D, Wragg K, Chen J, Wang H, Song J, Blin M, Bolding C, Vardaman D, Giles K, Tidwell H, Ali M, Janappareddi A, Wood S, Goldstein D. Clonally expanded memory CD8+ T cells accumulate in atherosclerotic plaques and are pro-atherogenic in aged mice. Nature Aging 2023, 3: 1576-1590. PMID: 37996758, PMCID: PMC11924142, DOI: 10.1038/s43587-023-00515-w.Peer-Reviewed Original ResearchConceptsT cellsMemory CD8Aged miceAtherosclerotic plaquesDepletion of CD8Effector memory subsetsStrong risk factorT cell activationEnhanced atherosclerosisSplenic CD8Adoptive transferDonor miceMemory subsetsRecipient miceRisk factorsCD8Therapeutic targetCell activationAtherosclerosisSingle-cell RNA sequencingMiceTranscriptomic signaturesAtherogenesisPlaquesRNA sequencingCirculating T cell specific extracellular vesicle profiles in cardiac allograft acute cellular rejection
Korutla L, Hoffman J, Rostami S, Hu R, Korutla V, Markmann C, Mullan C, Sotolongo A, Habertheuer A, Romano C, Acker M, Sen S, Agarwal D, Jayaraman A, Li B, Davis M, Naji A, Vallabhajosyula P. Circulating T cell specific extracellular vesicle profiles in cardiac allograft acute cellular rejection. American Journal Of Transplantation 2023, 24: 419-435. PMID: 38295008, DOI: 10.1016/j.ajt.2023.10.021.Peer-Reviewed Original ResearchAcute cellular rejectionAllogeneic transplant recipientsTransplant recipientsCellular rejectionHeart transplantationAlloreactive T cell activationEarly acute cellular rejectionT-cell receptor sequencingSyngeneic transplant recipientsCell receptor sequencingClinical heart transplantationT cell clonesNovel candidate biomarkersT cell activationQuantitative RT-PCRRecipient circulationOrgan transplantationT cellsVesicle profilesNoninvasive biomarkersCandidate biomarkersCell activationRegulatory markersDonor cardiomyocytesTransplantationEffects of anti‐tau immunotherapy on reactive microgliosis, cerebral endotheliopathy, and cognitive function in an experimental model of cerebral malaria
Ndunge O, Shikani H, Dai M, Freeman B, Desruisseaux M. Effects of anti‐tau immunotherapy on reactive microgliosis, cerebral endotheliopathy, and cognitive function in an experimental model of cerebral malaria. Journal Of Neurochemistry 2023, 167: 441-460. PMID: 37814468, PMCID: PMC10596299, DOI: 10.1111/jnc.15972.Peer-Reviewed Original ResearchConceptsNeural cell injuryCerebral malariaExperimental CMCell injuryUninfected micePHF-1Cell activationNeurodegenerative diseasesAbnormal regulationExperimental modelAnti-tau immunotherapyTau-targeting therapiesExperimental cerebral malariaGlial cell activationPlasmodium berghei ANKAPlasmodium berghei NK65Abnormal tau phosphorylationSubsequent neurocognitive impairmentSignificant memory impairmentNeural cell damageMicrovascular congestionPbA infectionInflammatory markersBerghei ANKANeurological deficitsAtezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial
Monjazeb A, Daly M, Luxardi G, Maverakis E, Merleev A, Marusina A, Borowsky A, Mirhadi A, Shiao S, Beckett L, Chen S, Eastham D, Li T, Vick L, McGee H, Lara F, Garcia L, Morris L, Canter R, Riess J, Schalper K, Murphy W, Kelly K. Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. Nature Communications 2023, 14: 5332. PMID: 37658083, PMCID: PMC10474145, DOI: 10.1038/s41467-023-40813-w.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerStereotactic ablative radiotherapyEarly-stage non-small cell lung cancerCell lung cancerAblative radiotherapyLung cancerMulti-institutional phase I trialSingle-arm phase IThird of patientsPhase I trialEx vivo stimulationT cell activationInoperable patientsPrimary endpointSecondary endpointsEfficacy signalsI trialT cellsAdaptive immunityCell activationPatientsPhase IPhase IIIEarly responseAtezolizumabEndothelial VEGFR2-PLCγ signaling regulates vascular permeability and anti-tumor immunity through eNOS/Src
Sjöberg E, Melssen M, Richards M, Ding Y, Chanoca C, Chen D, Nwadozi E, Pal S, Love D, Ninchoji T, Shibuya M, Simons M, Dimberg A, Claesson-Welsh L. Endothelial VEGFR2-PLCγ signaling regulates vascular permeability and anti-tumor immunity through eNOS/Src. Journal Of Clinical Investigation 2023, 133: e161366. PMID: 37651195, PMCID: PMC10575733, DOI: 10.1172/jci161366.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseRenal cell carcinomaAnti-tumor immunityVascular leakageT cellsEndothelial barrierClear cell renal cell carcinomaCell renal cell carcinomaRegulatory T cellsHelper T cellsNitric oxide synthaseImmune cell activationAntitumor immunityImmunosuppressive cytokinesPoor prognosisCell carcinomaPLCγ pathwayOxide synthaseVascular permeabilityB cellsActivation of PLCγCell activationTumor vesselsDecreased expressionCancer forms
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