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 graftTargeting Host Complement C3a/C5a Receptors to Control of Acute Graft-Versus-Host Disease in Mice
Nguyen H, Heinrichs J, Fu J, Wu Y, Bastian D, Schutt S, Daenthanasanmak A, Dany M, Liu C, Fairlie D, Tomlinson S, Yu X. Targeting Host Complement C3a/C5a Receptors to Control of Acute Graft-Versus-Host Disease in Mice. Blood 2015, 126: 3076. DOI: 10.1182/blood.v126.23.3076.3076.Peer-Reviewed Original ResearchC3aR/C5aRAntigen presenting cellsDonor T cellsT cellsGVL activityHost diseaseC5aR signalingAlloreactive donor T cellsDonor T cell activationDonor T-cell responsesHost antigen presenting cellsAllogeneic hematopoietic cell transplantationComplement systemAcute Graft-VersusControl of GVHDHost hematopoietic cellsDevelopment of GVHDGVHD target organsAdaptive immune cellsHematopoietic cell transplantationEffector T cellsT cell responsesTotal body irradiationAlloreactive T cellsPro-inflammatory cytokinesHuman Mesenchymal Stromal Cells Attenuate Graft‐Versus‐Host Disease and Maintain Graft‐Versus‐Leukemia Activity Following Experimental Allogeneic Bone Marrow Transplantation
Auletta J, Eid S, Wuttisarnwattana P, Silva I, Metheny L, Keller M, Guardia‐Wolff R, Liu C, Wang F, Bowen T, Lee Z, Solchaga L, Ganguly S, Tyler M, Wilson D, Cooke K. Human Mesenchymal Stromal Cells Attenuate Graft‐Versus‐Host Disease and Maintain Graft‐Versus‐Leukemia Activity Following Experimental Allogeneic Bone Marrow Transplantation. Stem Cells 2015, 33: 601-614. PMID: 25336340, PMCID: PMC4304927, DOI: 10.1002/stem.1867.Peer-Reviewed Original ResearchConceptsT cell expansionT cell proliferationGraft-VersusHost diseaseLeukemia activityExperimental allogeneic bone marrow transplantationDonor T cell expansionAllogeneic bone marrow transplantationCytotoxic T cell activityAlloreactive T cell proliferationPotent GVL effectCyclo-oxygenase inhibitionT cell activityT cell suppressionBone marrow transplantationMarrow-derived mesenchymal stromal cellsSecondary lymphoid organsSplenic T cellsSplenic marginal zoneMixed leukocyte cultureMesenchymal stromal cellsBMT miceEP2 agonismGVL activityGVL effect
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 GVHD
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 approachesc‐Rel is an essential transcription factor for the development of acute graft‐versus‐host disease in mice
Yu Y, Wang D, Kaosaard K, Liu C, Fu J, Haarberg K, Anasetti C, Beg A, Yu X. c‐Rel is an essential transcription factor for the development of acute graft‐versus‐host disease in mice. European Journal Of Immunology 2013, 43: 2327-2337. PMID: 23716202, PMCID: PMC3940138, DOI: 10.1002/eji.201243282.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCell DifferentiationCell ProliferationForkhead Transcription FactorsGraft vs Host DiseaseImmune ToleranceLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutProto-Oncogene Proteins c-relTh1 CellsTh17 CellsT-Lymphocytes, RegulatoryTransplantation, HomologousConceptsT cellsAcute GVHDHost diseaseAllogeneic bone marrow transplantationAllogeneic hematopoietic cell transplantationC-RelGVHD target organsHematopoietic cell transplantationRegulatory T cellsBone marrow transplantationAcute graftLeukemia responseTransplant toleranceAllogeneic recipientsMarrow transplantationMinor histocompatibilityCell transplantationTh1 cellsLymphoid organsMurine modelTarget organsTherapeutic interventionsNF-κB familyGraftPotential targetPhosphatidylinositol 3-Kinase–Independent Signaling Pathways Contribute to ICOS-Mediated T Cell Costimulation in Acute Graft-Versus-Host Disease in Mice
Li J, Heinrichs J, Leconte J, Haarberg K, Semple K, Liu C, Gigoux M, Kornete M, Piccirillo C, Suh W, Yu X. Phosphatidylinositol 3-Kinase–Independent Signaling Pathways Contribute to ICOS-Mediated T Cell Costimulation in Acute Graft-Versus-Host Disease in Mice. The Journal Of Immunology 2013, 191: 200-207. PMID: 23729441, PMCID: PMC4318500, DOI: 10.4049/jimmunol.1203485.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsDisease Models, AnimalGene Knock-In TechniquesGraft vs Host DiseaseInducible T-Cell Co-Stimulator ProteinLymphocyte ActivationMiceMice, 129 StrainMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, TransgenicPhosphatidylinositol 3-KinaseSignal TransductionT-Lymphocyte SubsetsConceptsCD8 T cellsCD4 T cellsT cellsHost diseaseWild-type CD8 T cellsCD8 T cell compartmentAllogeneic bone marrow transplantationAcute Graft-VersusPathogenic potentialTotal T cellsAlloreactive T cellsBone marrow transplantationT cell compartmentWild-type T cellsIntracellular calcium mobilizationVivo pathogenic potentialT cell costimulationT cell activationKnockout T cellsAcute graftAcute GVHDGraft-VersusSevere GVHDGVHD modelMarrow transplantationAdoptively 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 linesHost-derived CD8+ dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation
Toubai T, Sun Y, Luker G, Liu J, Luker K, Tawara I, Evers R, Liu C, Mathewson N, Malter C, Nieves E, Choi S, Murphy K, Reddy P. Host-derived CD8+ dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation. Blood 2013, 121: 4231-4241. PMID: 23520337, PMCID: PMC3656455, DOI: 10.1182/blood-2012-05-432872.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsTumor-specific antigensGVT responseAllo-HCTAPC subsetsDendritic cellsExperimental allogeneic bone marrow transplantationHost-derived antigen-presenting cellsAllogeneic bone marrow transplantationAllogeneic hematopoietic cell transplantationAlloantigen-specific responsesHost-derived CD8Donor T cellsHematopoietic cell transplantationBone marrow transplantationRelevant murine modelStimulation of TLR3Host diseaseTumor effectMarrow transplantationCell transplantationTumor responseSerious toxicityT cellsOptimal graft
2012
T-Bet Is Critical for the Development of Acute Graft-Versus-Host Disease Through Controlling T Cell Differentiation and Function
Fu J, Wang D, Yu Y, Kaosaard K, Liu C, Anasetti C, Yu X. T-Bet Is Critical for the Development of Acute Graft-Versus-Host Disease Through Controlling T Cell Differentiation and Function. Blood 2012, 120: 452. DOI: 10.1182/blood.v120.21.452.452.Peer-Reviewed Original ResearchDonor T cellsHematopoietic cell transplantationAllogeneic hematopoietic cell transplantationInduction of GVHDGVHD target organsT cell infiltrationCD4 T cellsTh17 cellsT-betT cellsAcute GVHDHost diseaseAdoptive transferTh1 cellsCell infiltrationMurine allogeneic bone marrow transplantation modelTarget organsAllogeneic bone marrow transplantation modelWT CD4 T cellsIFN-γ KO miceBALB/c miceLess body weight lossTranscription factor T-betT-box transcription factor T-betAcute Graft-VersusInfluence of Donor Microbiota on the Severity of Experimental Graft-versus-Host-Disease
Tawara I, Liu C, Tamaki H, Toubai T, Sun Y, Evers R, Nieves E, Mathewson N, Nunez G, Reddy P. Influence of Donor Microbiota on the Severity of Experimental Graft-versus-Host-Disease. Transplantation And Cellular Therapy 2012, 19: 164-168. PMID: 22982686, PMCID: PMC3529780, DOI: 10.1016/j.bbmt.2012.09.001.Peer-Reviewed Original ResearchConceptsSeverity of GVHDDonor microbiotaHost diseaseT cellsT cell-mediated alloresponsesGerm-free donorsSeverity of graftAlloreactive T cellsRelevant murine modelImmune responseMurine modelRecipient microbiotaExperimental graftGVHDSeverityMicrobiotaRecent dataGraftMicrobial floraAlloresponsesCellsDiseaseInterleukin-22 Protects Intestinal Stem Cells from Immune-Mediated Tissue Damage and Regulates Sensitivity to Graft versus Host Disease
Hanash A, Dudakov J, Hua G, O’Connor M, Young L, Singer N, West M, Jenq R, Holland A, Kappel L, Ghosh A, Tsai J, Rao U, Yim N, Smith O, Velardi E, Hawryluk E, Murphy G, Liu C, Fouser L, Kolesnick R, Blazar B, van den Brink M. Interleukin-22 Protects Intestinal Stem Cells from Immune-Mediated Tissue Damage and Regulates Sensitivity to Graft versus Host Disease. Immunity 2012, 37: 339-350. PMID: 22921121, PMCID: PMC3477611, DOI: 10.1016/j.immuni.2012.05.028.Peer-Reviewed Original ResearchConceptsIL-23-responsive innate lymphoid cellsIntestinal IL-22IL-22Intestinal stem cellsTissue damageHost diseaseTransplant recipientsIL-22 deficiencyInflammatory intestinal damageDonor immune systemInnate lymphoid cellsBone marrow transplantIL-22 receptorStem cellsILC frequenciesPretransplant conditioningIntestinal damageMarrow transplantCrypt apoptosisLymphoid cellsImmune systemGVHDTissue sensitivityProtective factorsEpithelial integrityLBH589 Enhances T Cell Activation In Vivo and Accelerates Graft-versus-Host Disease in Mice
Wang D, Iclozan C, Liu C, Xia C, Anasetti C, Yu X. LBH589 Enhances T Cell Activation In Vivo and Accelerates Graft-versus-Host Disease in Mice. Transplantation And Cellular Therapy 2012, 18: 1182-1190.e1. PMID: 22698484, PMCID: PMC3417119, DOI: 10.1016/j.bbmt.2012.06.002.Peer-Reviewed Original ResearchConceptsBone marrow transplantSuberoylanilide hydroxamic acidAllogeneic bone marrow transplantAllogeneic transplant modelElevated Th1 cytokinesPrevention of GVHDDonor T cellsT cell infiltrationHistone deacetylase inhibitorsT cell activationTumor cell growthCXCR3 expressionHost diseaseRecipient serumPan-HDACiTh1 cytokinesMarrow transplantProinflammatory cytokinesTransplant modelCell infiltrationInflammatory diseasesGVHDT cellsMouse modelDisease ameliorationRegulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation
Jenq R, Ubeda C, Taur Y, Menezes C, Khanin R, Dudakov J, Liu C, West M, Singer N, Equinda M, Gobourne A, Lipuma L, Young L, Smith O, Ghosh A, Hanash A, Goldberg J, Aoyama K, Blazar B, Pamer E, van den Brink M. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. Journal Of Experimental Medicine 2012, 209: 903-911. PMID: 22547653, PMCID: PMC3348096, DOI: 10.1084/jem.20112408.Peer-Reviewed Original ResearchConceptsAllogeneic bone marrow transplantationBone marrow transplantationIntestinal inflammationMarrow transplantationAllogeneic BMT recipientsPotential risk factorsSubsequent GVHDHost diseaseBMT recipientsRisk factorsGVHDMouse modelResident gut microbesInflammationIntestinal microbiotaSignificant protectionGut floraHuman recipientsHuman floraInitial onsetGut microbesLongitudinal studyTransplantationMicrobiotaMiceDonor- but not host-derived interleukin-10 contributes to the regulation of experimental graft-versus-host disease
Tawara I, Sun Y, Liu C, Toubai T, Nieves E, Evers R, Alrubaie M, Mathewson N, Tamaki H, Reddy P. Donor- but not host-derived interleukin-10 contributes to the regulation of experimental graft-versus-host disease. Journal Of Leukocyte Biology 2012, 91: 667-675. PMID: 22262800, PMCID: PMC3317273, DOI: 10.1189/jlb.1011510.Peer-Reviewed Original ResearchConceptsSuppression of GVHDSeverity of GVHDIL-10Donor TregsBM graftsRegulation of GVHDImmune-regulatory cytokinesInterleukin-10 contributeAcute GVHDClinical GVHDGVHD severityHost diseaseDonor graftsGVHDPreclinical modelsTregsGene polymorphismsExperimental graftCellular subsetsGraftSeverityHost cellsFunctional relevanceHost tissuesIL
2011
Cross-Presentation by Host CD8α+dendritic Cells Augments Graft-Versus-Tumor Effect without Aggravating Graft-Versus-Host Disease After Allogeneic BMT
Toubai T, Sun Y, Tawara I, Liu C, Reddy P. Cross-Presentation by Host CD8α+dendritic Cells Augments Graft-Versus-Tumor Effect without Aggravating Graft-Versus-Host Disease After Allogeneic BMT. Blood 2011, 118: 310. DOI: 10.1182/blood.v118.21.310.310.Peer-Reviewed Original ResearchAntigen presenting cellsTumor-specific antigensProfessional antigen presenting cellsGVT responseAllogeneic animalsGraft-VersusSyngeneic B6APC subsetsTumor cellsPoly IToll-like receptor 3Induction of GVHDGVHD target organsWild-type B6Acute GVHDAllo-BMTCD8α- DCsAllogeneic BMTGVHD modelGVHD severityGVT effectHost diseaseTumor effectTLR-3Allo-antigenHost-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 levelsHost Basophils Are Dispensable for Induction of Donor T Helper 2 Cell Differentiation and Severity of Experimental Graft-versus-Host Disease
Tawara I, Nieves E, Liu C, Evers R, Toubai T, Sun Y, Alrubaie M, Reddy P. Host Basophils Are Dispensable for Induction of Donor T Helper 2 Cell Differentiation and Severity of Experimental Graft-versus-Host Disease. Transplantation And Cellular Therapy 2011, 17: 1747-1753. PMID: 21871863, PMCID: PMC3220796, DOI: 10.1016/j.bbmt.2011.08.013.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsAllogeneic bone marrow transplantationSeverity of GVHDBone marrow transplantationHost diseaseTh2 responsesMarrow transplantationDonor T cell proliferationDonor T-cell responsesInduction of graftT cell responsesT cell proliferationT helper 2 (Th2) cell differentiationTh2 polarizationLymphocyte responsesExperimental graftGVHDCell responsesBasophilsCell proliferationSeverityTransplantationGraftRecent dataDiseaseCeacam1 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