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 ResearchConceptsGraft-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
2015
RIG-I-Induced Type I IFNs Promote Regeneration of the Intestinal Stem Cell Compartment during Acute Tissue Damage
Fischer J, Bscheider M, Eisenkolb G, Wintges A, Lindemans C, Heidegger S, Monette S, Calafiore M, Rodriguez K, Lieberman S, Liu C, Peschel C, Docampo M, Velardi E, Jenq R, Hanash A, Dudakov J, Haas T, van den Brink M, Poeck H. RIG-I-Induced Type I IFNs Promote Regeneration of the Intestinal Stem Cell Compartment during Acute Tissue Damage. Blood 2015, 126: 3072. DOI: 10.1182/blood.v126.23.3072.3072.Peer-Reviewed Original ResearchTotal body irradiationEpithelial regenerationAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationAcute intestinal injuryEpithelial cellsIntestinal barrier damageStem cell transplantationAcute tissue damageType I IFNsType I IFNActivation of RIGInnovative therapeutic strategiesIntestinal epithelial cellsRegenerative functionMechanism of actionHost diseaseIntestinal injuryBody irradiationBarrier damageCell transplantationDeficient miceViral challengePreclinical modelsWorse graft
2014
IL-22 Is an Intestinal Stem Cell Growth Factor, and IL-22 Administration in Vivo Reduces Morbidity and Mortality in Murine GvHD
Lindemans C, Mertelsmann A, O’Connor M, Dudakov J, Jenq R, Velardi E, Young L, Smith O, Lawrence G, Luo N, Ivanov J, Hua G, Martin M, Liu C, Kolesnick R, Van Den Brink M, Hanash A. IL-22 Is an Intestinal Stem Cell Growth Factor, and IL-22 Administration in Vivo Reduces Morbidity and Mortality in Murine GvHD. Blood 2014, 124: 651. DOI: 10.1182/blood.v124.21.651.651.Peer-Reviewed Original ResearchInnate lymphoid cellsIL-22 administrationIL-22Small intestineLymphoid cellsGut GVHDGrowth factorAllogeneic hematopoietic stem cell transplantationDay sevenWild-type B6 miceHematopoietic stem cell transplantationStroma-derived growth factorsAllo-HSCT modelClinical GVHD scoresExpansion of Lgr5Post-transplant immunodeficiencyStem cell transplantationNumber of Lgr5Paneth cell numbersGut microbial floraCell growth factorMechanism of actionGVHD pathologyGVHD scoresReduces MorbidityA 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
Adoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity
Ghosh A, Dogan Y, Moroz M, Holland A, Yim N, Rao U, Young L, Tannenbaum D, Masih D, Velardi E, Tsai J, Jenq R, Penack O, Hanash A, Smith O, Piersanti K, Lezcano C, Murphy G, Liu C, Palomba M, Sauer M, Sadelain M, Ponomarev V, van den Brink M. Adoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity. Journal Of Clinical Investigation 2013, 123: 2654-2662. PMID: 23676461, PMCID: PMC3668849, DOI: 10.1172/jci66301.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntigen-Presenting CellsCell Line, TumorCytotoxicity, ImmunologicGraft RejectionGraft vs Host DiseaseHEK293 CellsHumansImmunotherapy, AdoptiveLeukemia, Lymphocytic, Chronic, B-CellMiceMice, Inbred BALB CMice, Inbred C57BLNeoplasm TransplantationT-LymphocytesTNF-Related Apoptosis-Inducing LigandConceptsGVT responseT cellsAllo-HSCTAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationCellular therapyAbsence of GVHDDR5-dependent mannerDonor T cellsAlloreactive T cellsStem cell transplantationChronic lymphocytic leukemia cellsPrecursor T cellsThird-party donorsLymphocytic leukemia cellsApoptosis-inducing ligandGVT activityHost diseaseCell transplantationCurative potentialTumor responseGVHDCertain malignanciesMouse modelHuman leukemia cell lines
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
2008
A Role for TNF Receptor Type II in Leukocyte Infiltration into the Lung during Experimental Idiopathic Pneumonia Syndrome
Hildebrandt G, Olkiewicz K, Corrion L, Clouthier S, Pierce E, Liu C, Cooke K. A Role for TNF Receptor Type II in Leukocyte Infiltration into the Lung during Experimental Idiopathic Pneumonia Syndrome. Transplantation And Cellular Therapy 2008, 14: 385-396. PMID: 18342780, PMCID: PMC2390587, DOI: 10.1016/j.bbmt.2008.01.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBronchoalveolar Lavage FluidFemaleGraft SurvivalGraft vs Host DiseaseLungMiceMice, Inbred C57BLMice, Inbred StrainsPneumoniaReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IIStem Cell TransplantationSyndromeTransplantation, HomologousTumor Necrosis Factor-alphaConceptsIdiopathic pneumonia syndromeTNF-alphaPneumonia syndromeAllo-SCTLeukocyte infiltrationPulmonary vascular endothelial cell apoptosisBronchoalveolar lavage fluid levelsExperimental Idiopathic Pneumonia SyndromePulmonary ICAM-1 expressionWild-type B6 miceAllogeneic stem cell transplantationTNF receptor type IIType II TNF receptorLavage fluid levelsStem cell transplantationICAM-1 expressionVascular endothelial cell apoptosisReceptor type IIMHC class IEndothelial cell apoptosisDonor leukocytesFatal complicationPulmonary inflammationSyngeneic donorsWT mice
2007
β2 integrins separate graft-versus-host disease and graft-versus-leukemia effects
Liang Y, Liu C, Djeu J, Zhong B, Peters T, Scharffetter-Kochanek K, Anasetti C, Yu X. β2 integrins separate graft-versus-host disease and graft-versus-leukemia effects. Blood 2007, 111: 954-962. PMID: 17928532, PMCID: PMC2200850, DOI: 10.1182/blood-2007-05-089573.Peer-Reviewed Original ResearchConceptsT cellsHost diseaseLeukemia effectMurine allogeneic bone marrow transplantation modelAllogeneic bone marrow transplantation modelWild-type donor T cellsAllogeneic hematopoietic stem cell transplantationDonor T-cell infiltrationDonor-derived T cellsHematopoietic stem cell transplantationBeta2 integrinsAnalysis of alloreactivityLess GVHD morbidityDevelopment of GVHDDonor T cellsGVHD target organsT cell infiltrationBone marrow transplantation modelStem cell transplantationWT T cellsT cell activationGVHD morbidityGVL activityGVL effectLess GVHDCCR1/CCL5 (RANTES) receptor-ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation
Choi S, Hildebrandt G, Olkiewicz K, Hanauer D, Chaudhary M, Silva I, Rogers C, Deurloo D, Fisher J, Liu C, Adams D, Chensue S, Cooke K. CCR1/CCL5 (RANTES) receptor-ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation. Blood 2007, 110: 3447-3455. PMID: 17641205, PMCID: PMC2200916, DOI: 10.1182/blood-2007-05-087403.Peer-Reviewed Original ResearchConceptsStem cell transplantationT cell responsesCCR1 expressionHost diseaseT cellsAllogeneic T-cell responsesAllogeneic stem cell transplantationCCR1-deficient miceDevelopment of GVHDCytolytic effector functionDonor cellsT cell functionChemokine receptor-ligand interactionsT cell proliferationHost target tissuesReceptor-ligand interactionsActivated T cellsAcute graftGVHD mortalityGVL activityIFNgamma secretionAllo-SCTGVHD severityLeukemic infiltrationLeukemic relapse288: A small molecular weight antagonist of CXCR3 reduces the severity of experimental idiopathic pneumonia syndrome and improves survival following allogeneic stem cell transplantation
Deurloo D, Chaudhary M, Olkiewicz K, Silva I, Choi S, Liu C, Collins T, Sullivan T, Cooke K. 288: A small molecular weight antagonist of CXCR3 reduces the severity of experimental idiopathic pneumonia syndrome and improves survival following allogeneic stem cell transplantation. Transplantation And Cellular Therapy 2007, 13: 105. DOI: 10.1016/j.bbmt.2006.12.293.Peer-Reviewed Original Research
2005
Absence of β7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine
Waldman E, Lu S, Hubbard V, Kochman A, Eng J, Terwey T, Muriglan S, Kim T, Heller G, Murphy G, Liu C, Alpdogan O, van den Brink M. Absence of β7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine. Blood 2005, 107: 1703-1711. PMID: 16291587, PMCID: PMC1895413, DOI: 10.1182/blood-2005-08-3445.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantationLess GVHD morbidityT cell infiltrationT cellsGVHD morbidityGVT activityHost diseaseDonor T-cell infiltrationDonor T cellsAlloreactive T cellsStem cell transplantationWild-type T cellsOverall significant decreaseIntestinal graftIntestinal GVHDLess graftBeta7 integrinCell transplantationCytokine productionAlpha4beta7 integrinIntact activationTumor experimentsMorbidityClinical potentialGraftCCR2 is required for CD8-induced graft-versus-host disease
Terwey T, Kim T, Kochman A, Hubbard V, Lu S, Zakrzewski J, Ramirez-Montagut T, Eng J, Muriglan S, Heller G, Murphy G, Liu C, Budak-Alpdogan T, Alpdogan O, van den Brink M. CCR2 is required for CD8-induced graft-versus-host disease. Blood 2005, 106: 3322-3330. PMID: 16037386, PMCID: PMC1895329, DOI: 10.1182/blood-2005-05-1860.Peer-Reviewed Original ResearchConceptsCC chemokine receptor 2Hematopoietic stem cell transplantationDevelopment of GVHDT cellsT cell migrationHost diseaseAllogeneic hematopoietic stem cell transplantationDonor-derived T cellsControl of CD8Donor-derived CD8GVHD target organsMurine bone marrow transplantation modelBone marrow transplantation modelStem cell transplantationChemokine receptor 2IFN-gamma productionWild-type CD8Alloreactive proliferationDonor CD8GVHD morbidityGVT activityTumor effectMajor complicationsCCR2 signalingCell transplantationAbsence 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
Donor T-cell production of RANTES significantly contributes to the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation
Hildebrandt G, Olkiewicz K, Choi S, Corrion L, Clouthier S, Liu C, Serody J, Cooke K. Donor T-cell production of RANTES significantly contributes to the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation. Blood 2004, 105: 2249-2257. PMID: 15546955, DOI: 10.1182/blood-2004-08-3320.Peer-Reviewed Original ResearchConceptsIdiopathic pneumonia syndromeDevelopment of IPSAllogeneic stem cell transplantationDonor T cellsStem cell transplantationT cell responsesT cellsPneumonia syndromeAllo-SCTCell transplantationAlloreactive T cell responsesAllo-SCT recipientsInflammatory cell infiltrationT cell productionExpression of RANTESEnhanced mRNA expressionDonor leukocytesConditioning regimensLung injurySyngeneic controlsCell infiltrationChemokine ligandLeukocyte recruitmentRANTESTissue damageCCR1 Expression on Donor Leukocytes Is Critical to the Development of Graft Versus Host Disease after Allogeneic SCT.
Hildebrandt G, Choi S, Olkiewicz K, Chensue S, Liu C, Cooke K. CCR1 Expression on Donor Leukocytes Is Critical to the Development of Graft Versus Host Disease after Allogeneic SCT. Blood 2004, 104: 3067. DOI: 10.1182/blood.v104.11.3067.3067.Peer-Reviewed Original ResearchT cell responsesAllo-SCTCCR1 expressionDonor leukocytesHost diseaseT cellsCell responsesDonor T-cell responsesGraft Versus Host DiseaseAllogeneic stem cell transplantationSerum IFNγ levelsTranslocation of endotoxinVersus Host DiseaseDonor T cellsSeverity of GVHDDonor cellsClinical scoring systemStem cell transplantationT cell expansionAcute graftGVL effectSignificant GVHDTNFa levelsAllogeneic SCTClinical GVHDIL-13 - Predictor of or Protector from Acute Graft Versus Host Disease?.
Hildebrandt G, Olkiewicz K, Choi S, Corrion L, Liu C, McKenzie A, Cooke K. IL-13 - Predictor of or Protector from Acute Graft Versus Host Disease?. Blood 2004, 104: 3070. DOI: 10.1182/blood.v104.11.3070.3070.Peer-Reviewed Original ResearchBALB/c ILStem cell transplantationDonor T cellsIL-13T cellsC ILSyngeneic controlsTNFa levelsAllo-SCTHost diseaseTh2 cytokinesDonor cellsAcute Graft Versus Host DiseaseGraft Versus Host DiseaseAllogeneic stem cell transplantationTh1-type cytokine responseAltered cytokine milieuDay 100 survivalRecipients of ILTypical Th2 cytokineSeverity of GVHDVersus Host DiseaseIL-13 levelsIL-5 levelsPathogenesis of GVHDBlockade 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 injuryDonor T cell-derived TNF alpha regulates pulmonary chemokine expression and the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation
Hildebrandt G, Olkiewicz K, Corrion L, Chang Y, Liu C, Ferrara J, Cooke K. Donor T cell-derived TNF alpha regulates pulmonary chemokine expression and the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation. Transplantation And Cellular Therapy 2004, 10: 20. DOI: 10.1016/j.bbmt.2003.12.078.Peer-Reviewed Original ResearchAbrogation of the interactions between cxcr3 and its ligands MIG and IP-10 reduces the severity of idiopathic pneumonia syndrome after allogeneic stem cell transplantation
Hildebrandt G, Corrion L, Olkiewicz K, Liu C, Cooke K. Abrogation of the interactions between cxcr3 and its ligands MIG and IP-10 reduces the severity of idiopathic pneumonia syndrome after allogeneic stem cell transplantation. Transplantation And Cellular Therapy 2004, 10: 17-18. DOI: 10.1016/j.bbmt.2003.12.063.Peer-Reviewed Original ResearchAllogeneic stem cell transplantationIdiopathic pneumonia syndromeStem cell transplantationLigand MigPneumonia syndrome
2003
108A role for the P75 but not the P55 TNFα receptor in the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation
Cooke K, Olkiewicz K, Erickson N, Hildebrandt G, Liu C, Ferrara J. 108A role for the P75 but not the P55 TNFα receptor in the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation. Transplantation And Cellular Therapy 2003, 9: 97. DOI: 10.1016/s1083-8791(03)80109-x.Peer-Reviewed Original Research