2023
Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation
Seike K, Kiledal A, Fujiwara H, Henig I, Burgos da Silva M, van den Brink M, Hein R, Hoostal M, Liu C, Oravecz-Wilson K, Lauder E, Li L, Sun Y, Schmidt T, Shah Y, Jenq R, Dick G, Reddy P. Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation. Immunity 2023, 56: 353-368.e6. PMID: 36736321, DOI: 10.1016/j.immuni.2023.01.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDysbiosisGastrointestinal DiseasesGraft vs Host DiseaseHematopoietic Stem Cell TransplantationIntestinesMiceConceptsGraft-versus-host diseaseAmbient oxygen levelsGI graft-versus-host diseaseGut microbiome compositionMicrobiome-dependent mannerMicrobiome compositionMicrobial structureOxygen levelsIntestinal dysbiosisGraft-versus-host disease severityDysbiosisAllogeneic stem cell transplantationAnaerobic commensalsPathogenic T cellsStem cell transplantationIntestinal diseaseInflammatory bowel diseaseGastrointestinal (GI) diseasesCell transplantationIntestinal pathologyT cellsHostBowel diseaseHIF-1aIntestinal damage
2014
A Small-Molecule c-Rel Inhibitor Reduces Alloactivation of T Cells without Compromising Antitumor Activity
Shono Y, Tuckett A, Ouk S, Liou H, Altan-Bonnet G, Tsai J, Oyler J, Smith O, West M, Singer N, Doubrovina E, Pankov D, Undhad C, Murphy G, Lezcano C, Liu C, O'Reilly R, van den Brink M, Zakrzewski J. A Small-Molecule c-Rel Inhibitor Reduces Alloactivation of T Cells without Compromising Antitumor Activity. Cancer Discovery 2014, 4: 578-591. PMID: 24550032, PMCID: PMC4011979, DOI: 10.1158/2159-8290.cd-13-0585.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleGene Expression RegulationGraft vs Host DiseaseGraft vs Tumor EffectHematopoietic Stem Cell TransplantationHumansLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLProto-Oncogene Proteins c-relReceptors, Antigen, T-CellSmall Molecule LibrariesT-LymphocytesTransplantation, HomologousConceptsT cellsC-Rel activityAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationEffector T cellsRegulatory T cellsIL-2 levelsStem cell transplantationAntigen-specific cytotoxicityC-Rel-deficient T cellsC-RelHuman T cellsT cell receptor activationGut homingGVT activityImmunomodulatory therapyInhibitor administrationCell transplantationTumor activityImmune systemReceptor activationPharmaceutical inhibitionSmall molecule-based inhibitionAlloactivationBroad suppression
2013
Pharmacologic inhibition of PKCα and PKCθ prevents GVHD while preserving GVL activity in mice
Haarberg K, Li J, Heinrichs J, Wang D, Liu C, Bronk C, Kaosaard K, Owyang A, Holland S, Masuda E, Tso K, Blazar B, Anasetti C, Beg A, Yu X. Pharmacologic inhibition of PKCα and PKCθ prevents GVHD while preserving GVL activity in mice. Blood 2013, 122: 2500-2511. PMID: 23908466, PMCID: PMC3790515, DOI: 10.1182/blood-2012-12-471938.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell SeparationDisease Models, AnimalEnzyme InhibitorsFlow CytometryGraft vs Host DiseaseGraft vs Leukemia EffectHematopoietic Stem Cell TransplantationIsoenzymesLeukemiaLymphocyte ActivationLymphomaMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutProtein Kinase CProtein Kinase C-alphaProtein Kinase C-thetaT-LymphocytesConceptsHematopoietic cell transplantationDonor T cell proliferationAllogeneic hematopoietic cell transplantationT cell proliferationGVL activityGVL effectCytokine productionT cellsPharmacologic inhibitionChemokine/cytokine productionT-cell cytotoxicDonor T cellsPreclinical murine modelsPotential therapeutic targetT cell activationGVHD inductionGVHD preventionPrevents GVHDHost diseaseLeukemia effectSevere graftTherapeutic optionsCell transplantationEffective therapyPharmacologic approachesLong-Term In Vivo Imaging of Multiple Organs at the Single Cell Level
Chen B, Jiao Y, Zhang P, Sun A, Pitt G, Deoliveira D, Drago N, Ye T, Liu C, Chao N. Long-Term In Vivo Imaging of Multiple Organs at the Single Cell Level. PLOS ONE 2013, 8: e52087. PMID: 23300962, PMCID: PMC3534688, DOI: 10.1371/journal.pone.0052087.Peer-Reviewed Original Research
2011
Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice
Yu Y, Wang D, Liu C, Kaosaard K, Semple K, Anasetti C, Yu X. Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice. Blood 2011, 118: 5011-5020. PMID: 21856864, PMCID: PMC3208306, DOI: 10.1182/blood-2011-03-340315.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCells, CulturedCombined Modality TherapyGraft vs Host DiseaseGraft vs Leukemia EffectHematopoietic Stem Cell TransplantationLeukemiaMiceMice, Inbred C57BLMice, KnockoutMolecular Targeted TherapyNuclear Receptor Subfamily 1, Group F, Member 3T-Box Domain ProteinsTh1 CellsTh17 CellsTransplantation, HomologousConceptsHematopoietic cell transplantationGVL effectT-betT cellsTranscription factor T-betPrevention of GVHDDonor T cellsCD8 T cellsAmeliorated GVHDGVL activityNaive ThTh17 subsetAdoptive transferCell transplantationTh17 differentiationEffective therapyHematologic malignanciesAllogeneic hostsGVHDMajor MHCTh1Regulatory phenotypeSkewed differentiationTargeted disruptionRORγtPretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation
Hashimoto D, Chow A, Greter M, Saenger Y, Kwan W, Leboeuf M, Ginhoux F, Ochando J, Kunisaki Y, van Rooijen N, Liu C, Teshima T, Heeger P, Stanley E, Frenette P, Merad M. Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation. Journal Of Experimental Medicine 2011, 208: 1069-1082. PMID: 21536742, PMCID: PMC3092347, DOI: 10.1084/jem.20101709.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen-Presenting CellsFemaleGraft vs Host DiseaseHematopoietic Stem Cell TransplantationMacrophage Colony-Stimulating FactorMacrophagesMaleMiceMice, Inbred BALB CMice, KnockoutT-LymphocytesTransplantation, HomologousConceptsDonor allogeneic T cellsDonor T cell expansionAllogeneic hematopoietic cell transplantationAllogeneic T cellsHematopoietic cell transplantationAllo-HCTT cell expansionT cellsAcute GVHDCell transplantationHost macrophagesHost antigen-presenting cellsMacrophage poolPotential prophylactic therapyAlloreactive T cellsAntigen-presenting cellsAcute graftGVHD morbidityGVHD mortalityHost DCsHost diseaseProphylactic therapyRecipient miceGVHDRecipient macrophages
2010
Inhibition of Neovascularization to Simultaneously Ameliorate Graft-vs-Host Disease and Decrease Tumor Growth
Penack O, Henke E, Suh D, King C, Smith O, Na I, Holland A, Ghosh A, Lu S, Jenq R, Liu C, Murphy G, Lu T, May C, Scheinberg D, Gao D, Mittal V, Heller G, Benezra R, van den Brink M. Inhibition of Neovascularization to Simultaneously Ameliorate Graft-vs-Host Disease and Decrease Tumor Growth. Journal Of The National Cancer Institute 2010, 102: 894-908. PMID: 20463307, PMCID: PMC2886094, DOI: 10.1093/jnci/djq172.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAnimalsAntibodies, MonoclonalAntigens, CDBone Marrow TransplantationCadherinsFemaleFlow CytometryFluorescent Antibody TechniqueGraft vs Host DiseaseHematopoietic Stem Cell TransplantationMiceMice, Inbred C57BLNeoplasmsNeovascularization, PathologicTransplantation, HomologousConceptsTumor growthAllo-BMTHost diseaseAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationEndothelial cellsAllo-BMT recipientsGVHD target tissuesAllogeneic BM transplantationStem cell transplantationEndothelial progenitor cellsDecreases tumor growthInhibition of neovascularizationTumor-bearing miceTissue endothelial cellsAmeliorate graftDonor BMBM transplantationCell transplantationGVHDBone marrowTherapeutic targetingNeovascularizationOverall outcomeTumor vasculature
2005
Absence of inducible costimulator on alloreactive T cells reduces graft versus host disease and induces Th2 deviation
Hubbard V, Eng J, Ramirez-Montagut T, Tjoe K, Muriglan S, Kochman A, Terwey T, Willis L, Schiro R, Heller G, Murphy G, Liu C, Alpdogan O, van den Brink M. Absence of inducible costimulator on alloreactive T cells reduces graft versus host disease and induces Th2 deviation. Blood 2005, 106: 3285-3292. PMID: 15956289, PMCID: PMC1895338, DOI: 10.1182/blood-2005-01-0410.Peer-Reviewed Original ResearchConceptsAlloreactive T cellsInducible costimulatorT cellsHost diseaseInterleukin-4Allogeneic hematopoietic stem cell transplantationRole of ICOSHematopoietic stem cell transplantationLess GVHD morbidityTh2 immune deviationIL-10 levelsTh1/Th2 developmentMemory T cellsStem cell transplantationWild-type T cellsActivated T cellsCutaneous GVHDGVHD morbidityGVL activityHepatic GVHDImmune deviationLess GVHDTh2 deviationGVHD modelT helper
2004
Blockade of CXCR3 Receptor:Ligand Interactions Reduces Leukocyte Recruitment to the Lung and the Severity of Experimental Idiopathic Pneumonia Syndrome
Hildebrandt G, Corrion L, Olkiewicz K, Lu B, Lowler K, Duffner U, Moore B, Kuziel W, Liu C, Cooke K. Blockade of CXCR3 Receptor:Ligand Interactions Reduces Leukocyte Recruitment to the Lung and the Severity of Experimental Idiopathic Pneumonia Syndrome. The Journal Of Immunology 2004, 173: 2050-2059. PMID: 15265940, DOI: 10.4049/jimmunol.173.3.2050.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow CellsBronchoalveolar Lavage FluidCells, CulturedChemokine CXCL10Chemokine CXCL9Chemokines, CXCChemotaxis, LeukocyteCrosses, GeneticFemaleHematopoietic Stem Cell TransplantationInterferon-gammaLigandsLungLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutPneumoniaReceptors, CCR5Receptors, ChemokineReceptors, CXCR3SpleenT-Lymphocytes, CytotoxicTransplantation, HomologousTumor Necrosis Factor-alphaConceptsIdiopathic pneumonia syndromeDonor T cellsPneumonia syndromeIP-10TNF-alphaT cellsIFN-gammaCXCR3 receptorDevelopment of IPSExperimental Idiopathic Pneumonia SyndromeIP-10 protein levelsAllogeneic stem cell transplantationAllo-SCT recipientsInfiltration of IFNStandard immunosuppressive therapyT cell subsetsBronchoalveolar lavage fluidStem cell transplantationT cell recruitmentControl-treated animalsImmunosuppressive therapyLigand MigAllo-SCTFatal complicationLung injury