2015
IL-22 Directly Regulates Intestinal Stem Cells, Protecting Epithelium from GvHD and Reducing GvHD Mortality
Lindemans C, Mertelsmann A, O'Connor M, Calafiore M, Dudakov J, Jenq R, Velardi E, Young L, Smith O, Lawrence G, Luo N, Ivanov J, Hua G, Martin L, Liu C, Kolesnick R, van den Brink M, Hanash A. IL-22 Directly Regulates Intestinal Stem Cells, Protecting Epithelium from GvHD and Reducing GvHD Mortality. Transplantation And Cellular Therapy 2015, 21: s58-s59. DOI: 10.1016/j.bbmt.2014.11.058.Peer-Reviewed Original Research
2014
NLRP6 Expression By the Hosts Enhances the Severity of Experimental Graft-Versus-Host Disease (GVHD)
Toubai T, Tamaki H, Rossi C, Oravecz-Wilson K, Liu C, Mathewson N, Sun Y, Chen G, Reddy P. NLRP6 Expression By the Hosts Enhances the Severity of Experimental Graft-Versus-Host Disease (GVHD). Blood 2014, 124: 2421. DOI: 10.1182/blood.v124.21.2421.2421.Peer-Reviewed Original ResearchDonor T cellsT cellsGI tractGI GVHDWT B6GVHD severityImmune cellsCytokine secretionIntestinal epitheliumBALB/c donorsNOD-like receptor familyAlteration of microbiotaModel of GVHDGut microflora compositionBALB/c T cellsIL-18 secretionSplenic T cellsCertain immune cellsIntestinal epithelial cellsNon-hematopoietic cellsGVHD mortalityNLRP6 deficiencyAllogeneic recipientsDendritic cellsIntestinal inflammation
2013
Atypical E2F Dependent Dysregulation Of Cell Cycling By Microrna-142 Regulates T-Cell Responses and Experimental Graft-Versus-Host Disease
Sun Y, Oravecz-Wilson K, Saunders T, Wang Y, Toubai T, Mathewson N, Liu C, Hou G, Cummings E, Ross C, Reddy P. Atypical E2F Dependent Dysregulation Of Cell Cycling By Microrna-142 Regulates T-Cell Responses and Experimental Graft-Versus-Host Disease. Blood 2013, 122: 136. DOI: 10.1182/blood.v122.21.136.136.Peer-Reviewed Original ResearchT cell responsesKO T cellsWT T cellsT cellsGVHD mortalityCell responsesDay 7 post-BMTBALB/c animalsRatio of TregPeripheral blood examinationDonor T cellsT cell immunityBone marrow studyMiR-142Conventional T cellsLower IL-2Naïve T cellsSecondary lymphoid organsIL-6 productionSimilar absolute numbersNovel therapeutic strategiesT cell cyclingWT littermate controlsSignificant differencesImmune system function
2012
CD24-Siglec-G Interaction Plays an Important in Reducing Experimental Graft-Versus-Host Disease (GVHD)
Toubai T, Evers R, Sun Y, Tawara I, Liu C, Tamaki H, Mathewson N, Nieves E, Bassetti M, Zheng P, Liu Y, Reddy P. CD24-Siglec-G Interaction Plays an Important in Reducing Experimental Graft-Versus-Host Disease (GVHD). Blood 2012, 120: 453. DOI: 10.1182/blood.v120.21.453.453.Peer-Reviewed Original ResearchHost antigen presenting cellsAntigen presenting cellsBALB/c donorsT cellsWT B6Allogeneic BMTImmunoreceptor tyrosine-based inhibitory motifWorse survivalSerum levelsImmune activationBM chimerasDonor T cell expansionAllogeneic T-cell responsesT cell responsesBALB/c T cellsPro-inflammatory cytokinesT cell expansionRelevant murine modelRole of SiglecsC donorsIg-like lectinsIntensity of conditioningGraft-VersusGVHD mortalityHigher GVHD
2011
Donor but Not the Host Derived Interleukin-10 (IL-10) Contributes to Regulation of Graft-Versus-Host Disease (GVHD)
Tawara I, Sun Y, Liu C, Toubai T, Reddy P. Donor but Not the Host Derived Interleukin-10 (IL-10) Contributes to Regulation of Graft-Versus-Host Disease (GVHD). Blood 2011, 118: 2975. DOI: 10.1182/blood.v118.21.2975.2975.Peer-Reviewed Original ResearchT cell-depleted bone marrowT effector cellsDonor TregsIL-10B6 donorsEffector cellsAllogeneic animalsAcute GVHDDonor BMGVHD mortalityGVHD severityT effectorsT cellsNon-hematopoietic cellsWT B6B6 miceB6 animalsDonor regulatory T cellsT cell-depleted BMRegulation of GVHDSuppression of GVHDWT B6 miceIL-10 deficiencySeverity of GVHDIL-10 secretionHost-Derived IL-22 Limits Graft Versus Host Disease and Protects the Intestinal Stem Cell Niche
Hanash A, Dudakov J, Hua G, Young L, O'connor M, Jenq R, Holland A, Smith O, Liu C, Fouser L, Kolesnick R, Blazar B, Van Den Brink M. Host-Derived IL-22 Limits Graft Versus Host Disease and Protects the Intestinal Stem Cell Niche. Blood 2011, 118: 309. DOI: 10.1182/blood.v118.21.309.309.Peer-Reviewed Original ResearchInnate lymphoid cellsIL-22 deficiencyDonor immune responsesIL-22R expressionIL-22Post-BMTIntestinal stem cellsIntestinal epitheliumGVHD mortalityKO recipientsHost diseaseClinical GVHDT cellsImmune responseIL-22-producing innate lymphoid cellsGraft Versus Host DiseaseIL-22 KO miceLarge intestineMurine bone marrow transplantationHost hematopoietic cellsTarget of GVHDVersus Host DiseaseIL-22 productionDonor immune systemIL-22 levelsCeacam1 Separates Graft-versus-Host-Disease from Graft-versus-Tumor Activity after Experimental Allogeneic Bone Marrow Transplantation
Lu S, Kappel L, Charbonneau-Allard A, Atallah R, Holland A, Turbide C, Hubbard V, Rotolo J, Smith M, Suh D, King C, Rao U, Yim N, Bautista J, Jenq R, Penack O, Na I, Liu C, Murphy G, Alpdogan O, Blumberg R, Macian F, Holmes K, Beauchemin N, van den Brink M. Ceacam1 Separates Graft-versus-Host-Disease from Graft-versus-Tumor Activity after Experimental Allogeneic Bone Marrow Transplantation. PLOS ONE 2011, 6: e21611. PMID: 21760897, PMCID: PMC3130781, DOI: 10.1371/journal.pone.0021611.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCarcinoembryonic AntigenCD8-Positive T-LymphocytesCell PolarityCell ProliferationCytotoxicity, ImmunologicDendritic CellsGraft vs Host DiseaseGraft vs Tumor EffectHumansIntegrinsIntestine, SmallLymphocyte ActivationLymphocyte CountLymphoid TissueMiceOrgan SpecificityRadiation Injuries, ExperimentalRadiation, IonizingTransplantation, HomologousConceptsAllogeneic bone marrow transplantationBone marrow transplantationDonor T cellsCD8 T cellsT cellsMarrow transplantationGVHD mortalityTumor activityExperimental allogeneic bone marrow transplantationInflammatory bowel disease modelCell adhesion molecule-1GVHD target tissuesRegulation of GVHDTarget tissuesT cell numbersAlloreactive T cellsAdhesion molecule-1T cell activationVariety of physiologicAllo-BMTSystemic GVHDHost diseaseSmall intestinal cryptsDonor graftsAllogeneic transplantationPretransplant 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 ResearchConceptsDonor 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
Absence of P-Selectin in Recipients of Allogeneic Bone Marrow Transplantation Ameliorates Experimental Graft-versus-Host Disease
Lu S, Holland A, Na I, Terwey T, Alpdogan O, Bautista J, Smith O, Suh D, King C, Kochman A, Hubbard V, Rao U, Yim N, Liu C, Laga A, Murphy G, Jenq R, Zakrzewski J, Penack O, Dykstra L, Bampoe K, Perez L, Furie B, Furie B, van den Brink M. Absence of P-Selectin in Recipients of Allogeneic Bone Marrow Transplantation Ameliorates Experimental Graft-versus-Host Disease. The Journal Of Immunology 2010, 185: 1912-1919. PMID: 20622117, PMCID: PMC3752704, DOI: 10.4049/jimmunol.0903148.Peer-Reviewed Original ResearchConceptsSecondary lymphoid organsDonor T cellsAllogeneic bone marrow transplantationAlloreactive T cellsBone marrow transplantationT cellsWT T cellsP-selectinP-selectin glycoprotein ligand-1P-selectin ligandsMarrow transplantationSmall bowelInflamed tissuesDonor alloreactive T cellsHost disease (GVHD) pathophysiologyGVHD target organsAlloactivated T cellsLigand 1Wild-type recipientsGVHD mortalityGVHD prophylaxisHost diseaseLymphoid organsPeyer's patchesExperimental disease
2009
A Crucial Role for Antigen Presenting Cells in Donor CD4+CD25+ Regulatory T Cell Mediated Suppression of Experimental Gvhd.
Tawara I, Toubai T, Malter C, Sun Y, Nieves E, Lowler K, Liu C, Ferrara J, Reddy P. A Crucial Role for Antigen Presenting Cells in Donor CD4+CD25+ Regulatory T Cell Mediated Suppression of Experimental Gvhd. Blood 2009, 114: 688. DOI: 10.1182/blood.v114.22.688.688.Peer-Reviewed Original ResearchHost antigen presenting cellsAntigen presenting cellsGVHD mortalityGVHD protectionT cellsWT recipientsIL-10Effector phaseDonor TregsExperimental GVHDAllo-antigenB6 animalsPresenting cellsClass IIProfessional antigen presenting cellsLack of TregsMaintenance of GVHDRegulation of GVHDResponse of TregsExpansion of CD8Target tissuesRegulatory T cellsT cell effectorsClass II expressionHost target tissues
2008
IL-17 contributes to CD4-mediated graft-versus-host disease
Kappel L, Goldberg G, King C, Suh D, Smith O, Ligh C, Holland A, Grubin J, Mark N, Liu C, Iwakura Y, Heller G, van den Brink M. IL-17 contributes to CD4-mediated graft-versus-host disease. Blood 2008, 113: 945-952. PMID: 18931341, PMCID: PMC2630280, DOI: 10.1182/blood-2008-08-172155.Peer-Reviewed Original ResearchConceptsRecipients of ILT cellsGVHD mortalityHost diseaseIL-17Proinflammatory cytokinesAllogeneic bone marrow transplantAllogeneic BMT modelIL-17 contributesDonor T cellsBone marrow transplantWhole T cellsT-cell recipientsAcute graftGVHD developmentGVT activityAllograft rejectionTh17 cellsIL-17FIL-22Interleukin-17Marrow transplantAutoimmune diseasesTh1 cellsLymphoid organsCombined Th2 cytokine deficiency in donor T cells aggravates experimental acute graft-vs-host disease
Tawara I, Maeda Y, Sun Y, Lowler K, Liu C, Toubai T, McKenzie A, Reddy P. Combined Th2 cytokine deficiency in donor T cells aggravates experimental acute graft-vs-host disease. Experimental Hematology 2008, 36: 988-996. PMID: 18410989, PMCID: PMC2603625, DOI: 10.1016/j.exphem.2008.02.010.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsBone Marrow TransplantationCD4-Positive T-LymphocytesCell ProliferationDisease Models, AnimalEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryGraft vs Host DiseaseImmunologic TestsInterleukin-2 Receptor alpha SubunitInterleukinsMajor Histocompatibility ComplexMiceMice, Inbred BALB CMice, Inbred C57BLSurvival RateTh2 CellsT-LymphocytesTransplantation, HomologousConceptsDonor T cellsT cellsWT T cellsTh2 cytokinesAcute graftAllogeneic bone marrow transplantationAllogeneic antigen-presenting cellsT cell proliferative responsesAnti-CD3 monoclonal antibodyEnhanced T cell proliferationExperimental acute graftNumber of immunoregulatoryTarget organ damageTh2 cytokine secretionBone marrow transplantationT helper 1Antigen-presenting cellsWild-type T cellsT cell proliferationGreater clinical severityBALB/cB6 recipientsGVHD mortalityHost diseaseIL-17Organ-derived dendritic cells have differential effects on alloreactive T cells
Kim T, Terwey T, Zakrzewski J, Suh D, Kochman A, Chen M, King C, Borsotti C, Grubin J, Smith O, Heller G, Liu C, Murphy G, Alpdogan O, van den Brink M. Organ-derived dendritic cells have differential effects on alloreactive T cells. Blood 2008, 111: 2929-2940. PMID: 18178870, PMCID: PMC2254543, DOI: 10.1182/blood-2007-06-096602.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationDendritic CellsGene Expression ProfilingGraft vs Host DiseaseHumansIntegrinsIsoantigensLigandsLipopolysaccharidesLiverLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLOligonucleotide Array Sequence AnalysisOrgan SpecificityPhenotypeReceptors, Lymphocyte HomingSelectinsSurvival RateT-LymphocytesUp-RegulationConceptsAlloreactive T cellsBone marrow transplantationDendritic cellsT cellsGVHD mortalityLymph nodesAlloreactive donor T cellsGut-draining lymph nodesLiver-derived dendritic cellsNaive allogeneic T cellsMurine bone marrow transplantationPathophysiology of GVHDTarget organ liverDonor T cellsInduction of graftAllogeneic T cellsPeripheral lymph nodesGut-homing phenotypeMurine BMT modelHost diseaseAdoptive transferHoming moleculesMarrow transplantationStimulatory capacityBMT model
2007
CCR1/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 relapseLymphopenia-induced proliferation of donor T cells reduces their capacity for causing acute graft-versus-host disease
Maeda Y, Tawara I, Teshima T, Liu C, Hashimoto D, Matsuoka K, Tanimoto M, Reddy P. Lymphopenia-induced proliferation of donor T cells reduces their capacity for causing acute graft-versus-host disease. Experimental Hematology 2007, 35: 274-286. PMID: 17258076, DOI: 10.1016/j.exphem.2006.10.010.Peer-Reviewed Original ResearchConceptsAllogeneic bone marrow transplantationDonor T cellsBone marrow transplantationLymphopenia-induced proliferationNaïve T cellsT cellsHost diseaseAcute GVHD severityAnti-tumor immunityT cell subsetsPhenotype T cellsMurine experimental modelAnti-tumor functionAcute graftGVHD mortalitySevere GVHDGVHD severityAllograft rejectionMarrow transplantationCell depletionCell subsetsGVHDBiochemical parametersExperimental modelGraft
2005
Critical role of host γδ T cells in experimental acute graft-versus-host disease
Maeda Y, Reddy P, Lowler K, Liu C, Bishop D, Ferrara J. Critical role of host γδ T cells in experimental acute graft-versus-host disease. Blood 2005, 106: 749-755. PMID: 15797996, PMCID: PMC1895173, DOI: 10.1182/blood-2004-10-4087.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdoptive TransferAnimalsBone Marrow TransplantationCD40 LigandCell AdhesionCell CommunicationDendritic CellsFemaleGraft vs Host DiseaseInterferon-gammaMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutReceptors, Antigen, T-Cell, gamma-deltaT-Lymphocyte SubsetsTransplantation, HomologousTumor Necrosis Factor-alphaConceptsGammadelta T cellsDendritic cellsT cellsHost diseaseAllostimulatory capacityAllogeneic bone marrow transplantation modelAllogeneic T cell proliferationDonor T cell expansionWild-type B6 recipientsHost antigen-presenting cellsTumor necrosis factor alphaExperimental acute graftWT dendritic cellsNormal dendritic cellsBone marrow transplantation modelBM transplant recipientsΓδ T cellsT cell expansionAntigen-presenting cellsNecrosis factor alphaT cell proliferationAcute graftAcute GVHDB6 recipientsGVHD mortality
2002
Pretreatment of donors with interleukin-18 attenuates acute graft-versus-host disease via STAT6 and preserves graft-versus-leukemia effects
Reddy P, Teshima T, Hildebrandt G, Williams D, Liu C, Cooke K, Ferrara J. Pretreatment of donors with interleukin-18 attenuates acute graft-versus-host disease via STAT6 and preserves graft-versus-leukemia effects. Blood 2002, 101: 2877-2885. PMID: 12433681, DOI: 10.1182/blood-2002-08-2566.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsBone Marrow TransplantationFemaleGraft vs Host DiseaseGraft vs Leukemia EffectHumansInterferon-gammaInterleukin-18Leukemia, ExperimentalMiceMice, Inbred BALB CMice, Inbred C57BLSTAT6 Transcription FactorSurvival RateTissue DonorsT-LymphocytesTrans-ActivatorsTransplantation, HomologousConceptsAllogeneic bone marrow transplantationBone marrow transplantationPretreatment of donorsIL-18Acute GVHDAcute graftHost diseaseLeukemia effectTransplant donorsCytotoxic T lymphocyte activityAcute GVHD mortalityIL-18 pretreatmentDonor T cellsT lymphocyte activityBM transplant recipientsIL-4 secretionSTAT6-dependent mechanismIL-18 treatmentGVHD mortalityGVL effectPreserves graftTransplant recipientsInterleukin-18Marrow transplantationBM donorsEnhanced allostimulatory activity of host antigen-presenting cells in old mice intensifies acute graft-versus-host disease
Ordemann R, Hutchinson R, Friedman J, Burakoff S, Reddy P, Duffner U, Braun T, Liu C, Teshima T, Ferrara J. Enhanced allostimulatory activity of host antigen-presenting cells in old mice intensifies acute graft-versus-host disease. Journal Of Clinical Investigation 2002, 109: 1249-1256. PMID: 11994414, PMCID: PMC150964, DOI: 10.1172/jci14793.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAntigen-Presenting CellsBone Marrow TransplantationCells, CulturedDisease Models, AnimalFemaleGraft vs Host DiseaseHumansIntestine, SmallKiller Cells, NaturalLipopolysaccharidesLymphocyte ActivationMiceMice, Inbred C57BLSurvival RateT-Lymphocyte SubsetsTransplantation ChimeraTransplantation, HomologousTumor Necrosis Factor-alphaConceptsAntigen-presenting cellsDonor T-cell responsesHost antigen-presenting cellsT cell responsesOld miceAcute graftAllogeneic BMTHost diseaseOlder recipientsBM chimerasBMT modelT cellsCell responsesBone marrow transplantation recipientsDonor T cellsMore TNF-alphaMarrow transplantation recipientsMurine BMT modelHitherto unsuspected mechanismAcute GVHDAllostimulatory activityGVHD mortalitySevere GVHDWorse GVHDYoung BMFlt3 ligand therapy for recipients of allogeneic bone marrow transplants expands host CD8α+ dendritic cells and reduces experimental acute graft-versus-host disease
Teshima T, Reddy P, Lowler K, KuKuruga M, Liu C, Cooke K, Ferrara J. Flt3 ligand therapy for recipients of allogeneic bone marrow transplants expands host CD8α+ dendritic cells and reduces experimental acute graft-versus-host disease. Blood 2002, 99: 1825-1832. PMID: 11861301, DOI: 10.1182/blood.v99.5.1825.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdjuvants, ImmunologicAnimalsBone Marrow TransplantationCD8 AntigensCell DivisionCoculture TechniquesDendritic CellsDisease Models, AnimalFemaleGraft vs Host DiseaseLymphocyte ActivationMembrane ProteinsMiceMice, Inbred C57BLSurvival RateT-LymphocytesTransplantation, HomologousConceptsDendritic cellsT cell responsesAcute graftHost diseaseDonor T-cell responsesAllogeneic bone marrow transplantationAllogeneic T-cell responsesAllogeneic bone marrow transplantExperimental acute graftHost dendritic cellsPoor stimulatory capacityNormal dendritic cellsAllogeneic T cellsBone marrow transplantationTreatment of miceBone marrow transplantFL treatmentAcute GVHDGVHD mortalityDC subsetsAllogeneic lymphocytesDC numbersMarrow transplantationLigand therapyMarrow transplant