2025
CCL21-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
2023
CCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma
Geraldo L, Garcia C, Xu Y, Leser F, Grimaldi I, de Camargo Magalhães E, Dejaegher J, Solie L, Pereira C, Correia A, De Vleeschouwer S, Tavitian B, Canedo N, Mathivet T, Thomas J, Eichmann A, Lima F. CCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma. Cellular And Molecular Life Sciences 2023, 80: 179. PMID: 37314567, PMCID: PMC10267017, DOI: 10.1007/s00018-023-04788-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCentral Nervous SystemChemokine CCL21GlioblastomaHumansMacrophagesMiceMicrogliaReceptors, CCR7Tumor MicroenvironmentConceptsMicroglia/macrophage recruitmentC chemokine receptor type 7CCL21-CCR7Central nervous systemMacrophage recruitmentTumor microenvironmentChemokine receptor type 7Fatal primary tumorMouse GBM modelsChemokine ligand 21Potential therapeutic targetVEGF-A productionTumor cell deathCCR7 expressionTherapeutic optionsPrimary tumorPoor survivalCurrent treatmentGBM patientsTumor cell migrationTherapeutic targetBrain cancerNervous systemChemotherapy resistanceLigand 21
2017
Intestinal type 1 regulatory T cells migrate to periphery to suppress diabetogenic T cells and prevent diabetes development
Yu H, Gagliani N, Ishigame H, Huber S, Zhu S, Esplugues E, Herold KC, Wen L, Flavell RA. Intestinal type 1 regulatory T cells migrate to periphery to suppress diabetogenic T cells and prevent diabetes development. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 10443-10448. PMID: 28894001, PMCID: PMC5625908, DOI: 10.1073/pnas.1705599114.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCell DifferentiationCell MovementCell ProliferationCell- and Tissue-Based TherapyDiabetes Mellitus, Type 1DysbiosisFemaleGastrointestinal MicrobiomeImmune ToleranceInterleukin-10IntestinesMiceMice, Inbred NODMice, KnockoutReceptors, CCR4Receptors, CCR5Receptors, CCR7T-Lymphocytes, RegulatoryConceptsRegulatory T cellsTr1 cellsT cellsIL-10-producing type 1 regulatory T cellsType 1 regulatory T cellsAntigen-specific Tr1 cellsGut-associated lymphoid tissueDouble reporter miceDiabetogenic T cellsEffector T cellsDevelopment of diabetesT cells migrateIL-10 signalingType 1 diabetes managementIL-10R.NOD miceIL-10Diabetes incidenceDiabetes developmentAutoimmune diseasesTCR transgenicTh1 cellsLymphoid tissueChemokine receptorsPreclinical models
2016
CCR7 expression alters memory CD8 T-cell homeostasis by regulating occupancy in IL-7– and IL-15–dependent niches
Jung YW, Kim HG, Perry CJ, Kaech SM. CCR7 expression alters memory CD8 T-cell homeostasis by regulating occupancy in IL-7– and IL-15–dependent niches. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 8278-8283. PMID: 27385825, PMCID: PMC4961181, DOI: 10.1073/pnas.1602899113.Peer-Reviewed Original ResearchConceptsC receptor 7Memory T cellsMemory CD8 T-cell homeostasisMemory CD8 T cellsCD8 T cell homeostasisCD8 T cellsT cellsT cell homeostasisIL-15IL-7Different memory T-cell subsetsMemory CD8 T cell poolCD8 T cell poolLymphocytic choriomeningitis virus infectionMemory T cell subsetsHomeostasis of effectorAcute viral infectionT cell poolT cell subsetsT cell zonesDendritic cellsLymph nodesPredominant cytokineReceptor 7Chemokine receptorsImmune Activation and HIV-Specific CD8+ T Cells in Cerebrospinal Fluid of HIV Controllers and Noncontrollers
Ganesh A, Lemongello D, Lee E, Peterson J, McLaughlin BE, Ferre AL, Gillespie GM, Fuchs D, Deeks SG, Hunt PW, Price RW, Spudich SS, Shacklett BL. Immune Activation and HIV-Specific CD8+ T Cells in Cerebrospinal Fluid of HIV Controllers and Noncontrollers. AIDS Research And Human Retroviruses 2016, 32: 791-800. PMID: 27019338, PMCID: PMC4971411, DOI: 10.1089/aid.2015.0313.Peer-Reviewed Original ResearchMeSH KeywordsADP-ribosyl Cyclase 1Anti-HIV AgentsAntiretroviral Therapy, Highly ActiveCD4 Lymphocyte CountCD8-Positive T-LymphocytesDisease ResistanceGene ExpressionHIV InfectionsHIV-1HLA-DR AntigensHost-Pathogen InteractionsHumansLeukocyte Common AntigensLymphocyte ActivationReceptors, CCR5Receptors, CCR7RNA, ViralViral LoadViremiaConceptsCentral nervous systemHIV controllersAntiretroviral therapyT cellsCerebrospinal fluidViral loadCopies/HIV-specific T cellsMajor histocompatibility complex class IActivation markers CD38CSF viral loadHIV-specific CD8Undetectable plasma viremiaExpression of CCR5Majority of HIVPlasma viral loadEffector memory cellsHIV-negative controlsHistocompatibility complex class IAbsence of therapyComplex class ILong-term controlPlasma viremiaElite controllersHIV infectionGraft Site Microenvironment Determines Dendritic Cell Trafficking Through the CCR7-CCL19/21 AxisDetermining Dendritic Cell Trafficking
Hua J, Stevenson W, Dohlman T, Inomata T, Tahvildari M, Calcagno N, Pirmadjid N, Sadrai Z, Chauhan S, Dana R. Graft Site Microenvironment Determines Dendritic Cell Trafficking Through the CCR7-CCL19/21 AxisDetermining Dendritic Cell Trafficking. Investigative Ophthalmology & Visual Science 2016, 57: 1457-1467. PMID: 27031839, PMCID: PMC4819620, DOI: 10.1167/iovs.15-17551.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementCells, CulturedChemokine CCL19Chemokine CCL21Corneal TransplantationDendritic CellsDisease Models, AnimalEnzyme-Linked Immunosorbent AssayFlow CytometryGene Expression RegulationGraft SurvivalMaleMiceMice, Inbred BALB CMice, Inbred C57BLReal-Time Polymerase Chain ReactionReceptors, CCR7RNAConceptsDraining lymph nodesAntigen-presenting cellsInflamed graft bedsBone marrow-derived dendritic cellsDendritic cellsDendritic cell traffickingGraft bedSite inflammationMouse model of corneal transplantationModel of corneal transplantationCell traffickingMature bone marrow-derived dendritic cellsMarrow-derived dendritic cellsCD11c+ dendritic cellsMature DC migrationCorneal transplantationDonor corneasGraft survivalLymph nodesCCR7 ligandsLigands CCL19DC migrationMouse modelTranswell migration assayFlow cytometry
2013
IL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8+ T cell responses to influenza A virus
Pang IK, Ichinohe T, Iwasaki A. IL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8+ T cell responses to influenza A virus. Nature Immunology 2013, 14: 246-253. PMID: 23314004, PMCID: PMC3577947, DOI: 10.1038/ni.2514.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationCell MovementDendritic CellsInfluenza A virusInterleukin-1Lymphocyte ActivationMembrane GlycoproteinsMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMyeloid Differentiation Factor 88Nerve Tissue ProteinsOrthomyxoviridae InfectionsReceptors, CCR7Receptors, Cell SurfaceReceptors, Interleukin-1Receptors, Pattern RecognitionSignal TransductionToll-Like Receptor 7
2008
Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells
Anderson BE, Taylor PA, McNiff JM, Jain D, Demetris AJ, Panoskaltsis-Mortari A, Ager A, Blazar BR, Shlomchik WD, Shlomchik MJ. Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells. Blood 2008, 111: 5242-5251. PMID: 18285547, PMCID: PMC2384145, DOI: 10.1182/blood-2007-09-107953.Peer-Reviewed Original ResearchConceptsSecondary lymphoid tissuesT cellsMemory phenotype CD4 T cellsEffector memory T cellsAllogeneic stem cell transplantationHost disease inductionCD4 T cellsMemory T cellsStem cell transplantationNaive T cellsT cell traffickingGVHD initiationMild GVHDHost diseaseTransplant recipientsTumor effectCell transplantationLymphoid tissueGVHDDisease inductionImmune responseCD62LCCR7Major causeGraftDevelopment of Immunogenic Tumor-Loaded Dendritic Cells Through Physical Perturbation and Apoptotic Cell Loading
Shen X, Berger CL, Tigelaar R, Edelson RL. Development of Immunogenic Tumor-Loaded Dendritic Cells Through Physical Perturbation and Apoptotic Cell Loading. Immunological Investigations 2008, 37: 798-821. PMID: 18991097, DOI: 10.1080/08820130802403358.Peer-Reviewed Original ResearchMeSH KeywordsAntigen PresentationAntigens, CDAntigens, NeoplasmApoptosisB7-1 AntigenCancer VaccinesCD8-Positive T-LymphocytesCell DifferentiationCell Line, TumorCytotoxicity, ImmunologicDendritic CellsHumansImmunoglobulinsLymphocyte ActivationLymphoma, T-CellMechanotransduction, CellularMembrane GlycoproteinsMonocytesPerforinReceptors, CCR7Silicon DioxideConceptsT cellsDendritic cellsAllogeneic T cell proliferationCD8 T cellsLevels of perforinChemokine receptor CCR7T cell proliferationApoptotic tumor cellsUniverse of antigensDC vaccinesImmunogenic tumorsImmature DCsReceptor CCR7TNF-alphaPassage of leukocytesIFN-gammaHuman monocytesMonocytesTumor cellsPotent inductionCell apoptosisPhenotypic conversionCell proliferationApoptotic cellsCells induces
2007
Dual Roles of IL-15 in Maintaining IL-7RαlowCCR7− Memory CD8+ T Cells in Humans via Recovering the Phosphatidylinositol 3-Kinase/AKT Pathway
Kim HR, Hwang KA, Kang I. Dual Roles of IL-15 in Maintaining IL-7RαlowCCR7− Memory CD8+ T Cells in Humans via Recovering the Phosphatidylinositol 3-Kinase/AKT Pathway. The Journal Of Immunology 2007, 179: 6734-6740. PMID: 17982063, DOI: 10.4049/jimmunol.179.10.6734.Peer-Reviewed Original ResearchMeSH KeywordsCD8-Positive T-LymphocytesCell ProliferationCell SurvivalEnzyme ActivationGene Expression RegulationHumansImmunologic MemoryInfectionsInterleukin-15Interleukin-2 Receptor beta SubunitInterleukin-7NeoplasmsPerforinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, Antigen, T-CellReceptors, CCR7Receptors, Interleukin-17Signal TransductionConceptsIL-15T cellsPI3K/Akt pathwayAkt pathwayIL-7Memory T cell survivalProliferation of ILIL-15 signalingHuman peripheral bloodT cell survivalEffector cytokinesMemory CD8Peripheral bloodEffector functionsIL-7REnhanced gene expressionProliferative functionIndependent mechanismsILTCR triggeringCell survivalSuch cellsSurvivalTranscriptional factorsDual role
2006
Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the development of tertiary lymphoid structures in the thyroid
Marinkovic T, Garin A, Yokota Y, Fu YX, Ruddle NH, Furtado GC, Lira SA. Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the development of tertiary lymphoid structures in the thyroid. Journal Of Clinical Investigation 2006, 116: 2622-2632. PMID: 16998590, PMCID: PMC1570377, DOI: 10.1172/jci28993.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB-LymphocytesCD3 ComplexCD4-Positive T-LymphocytesCell Adhesion MoleculesCell CommunicationCell MovementChemokine CCL21ChemokinesChemokines, CCDendritic CellsDNA-Binding ProteinsGene ExpressionGreen Fluorescent ProteinsInhibitor of Differentiation Protein 2Lymphoid TissueLymphotoxin-alphaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicReceptors, CCR7Receptors, ChemokineThyroid DiseasesThyroid Gland
2004
Age-associated changes in the frequency of naïve, memory and effector CD8+ T cells
Hong MS, Dan JM, Choi JY, Kang I. Age-associated changes in the frequency of naïve, memory and effector CD8+ T cells. Mechanisms Of Ageing And Development 2004, 125: 615-618. PMID: 15491679, DOI: 10.1016/j.mad.2004.07.001.Peer-Reviewed Original ResearchConceptsAge-associated changesT cell subsetsEffector CD8T cellsCell subsetsFrequencies of naïveFrequency of CD8Expression of CD45RAT cell functionEffector memoryPeripheral bloodCD8CM cellsDecreased frequencyCentral memoryFlow cytometryElderly peopleCell functionSimilar frequencyNaïveCellsCCR7CD45RABloodSubset
2000
Localization of Distinct Peyer's Patch Dendritic Cell Subsets and Their Recruitment by Chemokines Macrophage Inflammatory Protein (Mip)-3α, Mip-3β, and Secondary Lymphoid Organ Chemokine
Iwasaki A, Kelsall B. Localization of Distinct Peyer's Patch Dendritic Cell Subsets and Their Recruitment by Chemokines Macrophage Inflammatory Protein (Mip)-3α, Mip-3β, and Secondary Lymphoid Organ Chemokine. Journal Of Experimental Medicine 2000, 191: 1381-1394. PMID: 10770804, PMCID: PMC2193144, DOI: 10.1084/jem.191.8.1381.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceChemokine CCL19Chemokine CCL20Chemokines, CCChemotaxisDendritic CellsDNA PrimersFemaleGene ExpressionIn Situ HybridizationMacrophage Inflammatory ProteinsMiceMice, Inbred BALB CMicroscopy, ConfocalModels, BiologicalPeyer's PatchesReceptors, CCR6Receptors, CCR7Receptors, ChemokineRNA, MessengerSpleenConceptsDendritic cell subsetsInterfollicular regionsDC subsetsCell subsetsInflammatory proteinPeyer's patchesSecondary lymphoid organ chemokineChemokine macrophage inflammatory proteinSplenic DC subsetsSubepithelial dome regionDistinct dendritic cell subsetsRole of chemokinesT cell responsesMacrophage inflammatory proteinT-cell regionsFollicle-associated epitheliumMurine Peyer's patchesTranscriptase-polymerase chain reaction analysisFunctional CCR7Lymphoid DCsMIP-3βPP DCsMyeloid DCsCCR7 expressionPolymerase chain reaction analysis
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