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
T-Bet Is Critical for the Development of Acute Graft-Versus-Host Disease By Regulating Hematopoietic Antigen Presenting Cells
Fu J, Wu Y, Nguyen H, Heinrichs J, Schutt S, Liu C, Anasetti C, Yu X. T-Bet Is Critical for the Development of Acute Graft-Versus-Host Disease By Regulating Hematopoietic Antigen Presenting Cells. Blood 2014, 124: 846. DOI: 10.1182/blood.v124.21.846.846.Peer-Reviewed Original ResearchAntigen presenting cellsDonor T cellsT cell apoptosisAcute GVHDRecipient dendritic cellsDendritic cellsIFN-γ productionT-betT cellsWT T cellsT cell activationHost diseasePresenting cellsAllogeneic hematopoietic stem cell transplantationAPC functionAlloreactive donor T cellsDevelopment of aGVHDDonor T cell activationDonor T-cell responsesAllogeneic bone marrow transplantationHematopoietic stem cell transplantationTranscription factor T-betAcute Graft-VersusInduction of GVHDSevere acute GVHDIL-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
Depletion of Vascular Endothelial Progenitor Cells Inhibits Inflammation
Penack O, Henke E, Suh D, King C, Smith M, Na I, Holland A, Ghosh A, Lu S, Jenq R, Liu C, Murphy G, Lu T, May C, Scheinberg D, Gao D, Mittal V, Benezra R, Van Den Brink M. Depletion of Vascular Endothelial Progenitor Cells Inhibits Inflammation. Blood 2008, 112: 694. DOI: 10.1182/blood.v112.11.694.694.Peer-Reviewed Original ResearchDepletion of EPCsAllo-BMT recipientsEndothelial progenitor cellsDonor T cellsRole of EPCsDay of BMTGVHD target organsDonor BM cellsAllo-BMTT cellsTumor growthImproved survivalA20 lymphomaInflamed colonPeripheral bloodEndothelial cellsInflammatory diseasesBM cellsTarget organsBM-derived endothelial progenitor cellsAllogeneic hematopoietic stem cell transplantationDay 0Donor endothelial progenitor cellsAllogeneic bone marrow transplantationBALB/c recipients
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 GVHD
2005
CCR2 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