2024
CD74 promotes the formation of an immunosuppressive tumor microenvironment in triple-negative breast cancer in mice by inducing the expansion of tolerogenic dendritic cells and regulatory B cells.
Pellegrino B, David K, Rabani S, Lampert B, Tran T, Doherty E, Piecychna M, Meza-Romero R, Leng L, Hershkovitz D, Vandenbark A, Bucala R, Becker-Herman S, Shachar I. CD74 promotes the formation of an immunosuppressive tumor microenvironment in triple-negative breast cancer in mice by inducing the expansion of tolerogenic dendritic cells and regulatory B cells. PLOS Biology 2024, 22: e3002905. PMID: 39576827, DOI: 10.1371/journal.pbio.3002905.Peer-Reviewed Original ResearchTriple-negative breast cancerMacrophage migration inhibitory factorImmunosuppressive tumor microenvironmentTolerogenic dendritic cellsRegulatory B cellsChronic lymphocytic leukemiaTumor microenvironmentDendritic cellsImmune cellsB cellsBreast cancerInfiltration of immune cellsAggressive breast cancer subtypeMassive infiltration of immune cellsLevels of CD74Cytokine macrophage migration inhibitory factorBreast cancer subtypesMigration inhibitory factorBinding to CD74Naive BTol-DCsLymphocytic leukemiaTumor environmentMassive infiltrationCancer subtypesA small-molecule allele-selective transcriptional inhibitor of the MIF immune susceptibility locus
Li J, Leng L, Pantouris G, Manjula R, Piecychna M, Abriola L, Hu B, Lolis E, Armstrong M, Donnelly S, Bucala R. A small-molecule allele-selective transcriptional inhibitor of the MIF immune susceptibility locus. Journal Of Biological Chemistry 2024, 300: 107443. PMID: 38838773, PMCID: PMC11259703, DOI: 10.1016/j.jbc.2024.107443.Peer-Reviewed Original ResearchPromoter microsatellitesGene expressionMicrosatellite repeat numberMacrophage migration inhibitory factorLength-dependent mannerRNA expression analysisSusceptibility lociFunctional variantsSmall molecule inhibitorsExpression analysisPharmacogenomic developmentRepeat numberMicrosatelliteFunctional interactionsTranscription inhibitorInflammatory gene expressionMIF mRNA expressionCytokine macrophage migration inhibitory factorTranscriptionGenesProtein expressionMigration inhibitory factorExpressionInhibitory factorExpressing macrophages
2023
The SNP rs755622 is associated with immune activation in glioblastoma
Alban T, Grabowski M, Otvos B, Bayik D, Wang W, Zalavadia A, Makarav V, Troike K, McGraw M, Rabljenovic A, Lauko A, Neumann C, Roversi G, Waite K, Cioffi G, Patil N, Tran T, McCortney K, Steffens A, Diaz-Montero C, Brown J, Egan K, Horbinski C, Barnholtz-Sloan J, Rajappa P, Vogelbaum M, Bucala R, Chan T, Ahluwalia M, Lathia J. The SNP rs755622 is associated with immune activation in glioblastoma. JCI Insight 2023, 8: e160024. PMID: 37252795, PMCID: PMC10371339, DOI: 10.1172/jci.insight.160024.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorImmune activationCytokine macrophage migration inhibitory factorMigration inhibitory factorLactotransferrin (LTF) expressionLeukocyte infiltrationHallmark of glioblastomaImmune microenvironmentTreatment responseRs755622Inhibitory factorDrug resistanceGermline mutationsIntratumoral heterogeneityTumoral microenvironmentGermline SNPsGlioblastoma
2022
CD74 as a regulator of transcription in normal B cells
David K, Friedlander G, Pellegrino B, Radomir L, Lewinsky H, Leng L, Bucala R, Becker-Herman S, Shachar I. CD74 as a regulator of transcription in normal B cells. Cell Reports 2022, 41: 111572. PMID: 36323260, DOI: 10.1016/j.celrep.2022.111572.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorNormal B cellsB cellsCytokine macrophage migration inhibitory factorRegulators of transcriptionChronic lymphocytic leukemia cellsMigration inhibitory factorNovel therapeutic pathwaysInhibition of transcriptionLymphocytic leukemia cellsTumor suppressor geneTranscriptional regulatorsTranscription factorsTherapeutic pathwaysCLL cellsFuture treatmentIntracellular domainOncogenic transformationMalignant cellsInhibitory factorRegulatory functionsPromoter areaLeukemia cellsTranscriptionGenesCD74 ablation rescues type 2 diabetes mellitus-induced cardiac remodeling and contractile dysfunction through pyroptosis-evoked regulation of ferroptosis
Chen L, Yin Z, Qin X, Zhu X, Chen X, Ding G, Sun D, Wu NN, Fei J, Bi Y, Zhang J, Bucala R, Ren J, Zheng Q. CD74 ablation rescues type 2 diabetes mellitus-induced cardiac remodeling and contractile dysfunction through pyroptosis-evoked regulation of ferroptosis. Pharmacological Research 2022, 176: 106086. PMID: 35033649, DOI: 10.1016/j.phrs.2022.106086.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntigens, Differentiation, B-LymphocyteCell LineDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2FemaleFerroptosisGene ExpressionHistocompatibility Antigens Class IIHumansMacrophage Migration-Inhibitory FactorsMaleMice, KnockoutMiddle AgedMyocardial ContractionMyocardiumNLR Family, Pyrin Domain-Containing 3 ProteinOxidative StressOxygen ConsumptionPyroptosisRatsVentricular RemodelingConceptsHigh glucose/high fatMacrophage migration inhibitory factorCardiac remodelingContractile dysfunctionCell death domainGene Ontology termsInhibitors of MIFRecombinant macrophage migration inhibitory factorCytokine macrophage migration inhibitory factorType 2 diabetes mellitusOntology termsDeath domainLipid peroxidationGlobal metabolic defectsKEGG analysisPlasma MIF levelsInjection of streptozotocinMitochondrial defectsHigh-fat dietMigration inhibitory factorInhibitor of NLRP3Cell deathPrecise interplayMitochondrial dysfunctionCognate receptors
2021
CD74 is a regulator of hematopoietic stem cell maintenance
Becker-Herman S, Rozenberg M, Hillel-Karniel C, Gil-Yarom N, Kramer M, Barak A, Sever L, David K, Radomir L, Lewinsky H, Levi M, Friedlander G, Bucala R, Peled A, Shachar I. CD74 is a regulator of hematopoietic stem cell maintenance. PLOS Biology 2021, 19: e3001121. PMID: 33661886, PMCID: PMC7963458, DOI: 10.1371/journal.pbio.3001121.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntigens, Differentiation, B-LymphocyteBone Marrow CellsBone Marrow TransplantationCell LineageFemaleHealthy VolunteersHematopoietic Stem CellsHistocompatibility Antigens Class IIHumansIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMaleMiceMice, Inbred C57BLSignal TransductionConceptsMacrophage migration inhibitory factorHematopoietic stem cellsBone marrowCytokine macrophage migration inhibitory factorMigration inhibitory factorNumber of HSPCsTransplant protocolsCD18 expressionClinical transplantationInduced SurvivalCD74Inhibitory factorBM nicheCell surface receptorsSelf-renewal propertiesClinical insightsProgenitor cellsBlood cell lineagesSurface receptorsStem cellsHematopoietic stemCell lineagesCellsUndifferentiated cellsHematopoietic stem cell maintenance
2020
Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis
Wirtz TH, Reuken PA, Jansen C, Fischer P, Bergmann I, Backhaus C, Emontzpohl C, Reißing J, Brandt EF, Koenen MT, Schneider KM, Schierwagen R, Brol MJ, Chang J, Zimmermann HW, Köse-Vogel N, Eggermann T, Kurth I, Stoppe C, Bucala R, Bernhagen J, Praktiknjo M, Stallmach A, Trautwein C, Trebicka J, Bruns T, Berres ML. Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis. JHEP Reports 2020, 3: 100221. PMID: 33659891, PMCID: PMC7890204, DOI: 10.1016/j.jhepr.2020.100221.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorConcentrations of MIFMigration inhibitory factorTransplant-free survivalAcute decompensationInhibitory factorSystemic inflammationReceptor CD74Serum concentrationsHigher macrophage migration inhibitory factorTransjugular intrahepatic portosystemic shunt insertionInflammatory cytokine macrophage migration inhibitory factorCytokine macrophage migration inhibitory factorHigher MIF concentrationsRight atrial bloodWorsening of ascitesChronic liver failureLiver function parametersShort-term mortalityHigher serum levelsMIF promoter polymorphismsRisk of deathPortal venous bloodInnate immune responseClassical scoring systems
2019
IMMU-28. TARGETING IMMUNOSUPPRESSIVE MYELOID DERIVED SUPPRESSOR CELLS VIA MIF/CD74 SIGNALING AXIS TO ATTENUATE GBM GROWTH
Alban T, Bayik D, Otvos B, Grabowski M, Ahluwalia M, Bucala R, Vogelbaum M, Lathia J. IMMU-28. TARGETING IMMUNOSUPPRESSIVE MYELOID DERIVED SUPPRESSOR CELLS VIA MIF/CD74 SIGNALING AXIS TO ATTENUATE GBM GROWTH. Neuro-Oncology 2019, 21: vi125-vi125. PMCID: PMC6847354, DOI: 10.1093/neuonc/noz175.521.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorTumor growthTumor microenvironmentMIF receptorM-MDSCsCytokine macrophage migration inhibitory factorGeneration of MDSCsTumor-infiltrating MDSCsMigration inhibitory factorMCP-1 secretionPersistent tumor growthImmune cell recognitionFuture clinical assessmentImmunosuppressive myeloidMDSC generationMDSC inhibitionMonocytic MDSCsPotent immunosuppressionMDSC functionSuppressor cellsImmunosuppressive microenvironmentImmune suppressionPoor prognosisImmune cellsCo-culture systemMIF and MIF2 have distinct but synergistic roles in CIA pathogenesis
Doherty E, Tilstam P, Bucala R. MIF and MIF2 have distinct but synergistic roles in CIA pathogenesis. The Journal Of Immunology 2019, 202: 180.13-180.13. DOI: 10.4049/jimmunol.202.supp.180.13.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorRheumatoid arthritisT cellsCIA inductionCollagen-induced arthritis (CIA) mouse modelSevere erosive rheumatoid arthritisEffector memory T cellsCytokine macrophage migration inhibitory factorRelapsing autoimmune diseaseErosive rheumatoid arthritisProgressive joint destructionT cell infiltrationMemory T cellsAbstract Rheumatoid arthritisArthritis mouse modelSecondary lymphoid organsMigration inhibitory factorCIA pathogenesisHigh expression alleleJoint inflammationJoint destructionLymph nodesWT miceAutoimmune diseasesReceptor CD74
2017
Adoptive transfer of a novel MIF receptor (CD74+) expressing memory T cell subpopulation is sufficient to transfer inflammatory arthritis
Doherty E, Piecychna M, Leng L, Bucala R. Adoptive transfer of a novel MIF receptor (CD74+) expressing memory T cell subpopulation is sufficient to transfer inflammatory arthritis. The Journal Of Immunology 2017, 198: 156.3-156.3. DOI: 10.4049/jimmunol.198.supp.156.3.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorEffector memory T cellsMemory T cellsRheumatoid arthritisT cellsJoint inflammationAdoptive transferCollagen-induced arthritis (CIA) mouse modelSevere erosive rheumatoid arthritisCytokine macrophage migration inhibitory factorMemory T-cell subpopulationsAutoimmune joint inflammationImmune checkpoints CTLA4MIF receptor CD74Effector memory phenotypeErosive rheumatoid arthritisAbstract Rheumatoid arthritisArthritis mouse modelT cell subpopulationsMigration inhibitory factorT cell activationExpression of STAT4High expression alleleInflammatory arthritisMIF receptor
2001
Neuroendocrine properties of macrophage migration inhibitory factor (MIF)
Fingerle‐Rowson G, Bucala R. Neuroendocrine properties of macrophage migration inhibitory factor (MIF). Immunology And Cell Biology 2001, 79: 368-375. PMID: 11488984, DOI: 10.1046/j.1440-1711.2001.01024.x.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorMigration inhibitory factorInhibitory factorCytokine macrophage migration inhibitory factorPro-inflammatory actionsMIF expressionSeptic shockNeuroendocrine mediatorsInflammatory diseasesPathogenic roleEndocrine circuitsNeuroendocrine propertiesImmune systemEndocrine tissuesImmune tissuesNeuroendocrine mechanismsDiseaseTissueArthritisNeuroendocrineFactorsPurification and Characterization of Macrophage Migration Inhibitory Factor as a Secretory Protein from Rat Epididymis: Evidences for Alternative Release and Transfer to Spermatozoa
Eickhoff R, Wilhelm B, Renneberg H, Wennemuth G, Bacher M, Linder D, Bucala R, Seitz J, Meinhardt A. Purification and Characterization of Macrophage Migration Inhibitory Factor as a Secretory Protein from Rat Epididymis: Evidences for Alternative Release and Transfer to Spermatozoa. Molecular Medicine 2001, 7: 27-35. PMID: 11474125, PMCID: PMC1949991, DOI: 10.1007/bf03401836.Peer-Reviewed Original ResearchConceptsOuter dense fibersSequence analysisDense fibersSecretion modeCDNA fragmentsN-terminal signal sequenceEndoplasmic reticulumMacrophage migration inhibitory factorEpithelial cellsCytokine macrophage migration inhibitory factorN-terminal amino acid sequence analysisAmino acid sequence analysisApical cell surfaceAcid sequence analysisEpididymal epithelial cellsRat epididymisSignal sequenceCDNA sequenceWestern blot experimentsPlasma membraneMigration inhibitory factorSecretory proteinsCytoskeletal elementsExpression patternsN-terminus
1999
Macrophage migration inhibitory factor in rheumatoid arthritis: Evidence of proinflammatory function and regulation by glucocorticoids
Leech M, Metz C, Hall P, Hutchinson P, Gianis K, Smith M, Weedon H, Holdsworth S, Bucala R, Morand E. Macrophage migration inhibitory factor in rheumatoid arthritis: Evidence of proinflammatory function and regulation by glucocorticoids. Arthritis & Rheumatism 1999, 42: 1601-1608. PMID: 10446857, DOI: 10.1002/1529-0131(199908)42:8<1601::aid-anr6>3.0.co;2-b.Peer-Reviewed Original ResearchMeSH KeywordsAgedArthritis, RheumatoidCells, CulturedCytokinesGlucocorticoidsHumansImmunohistochemistryInterferon-gammaLymphocyte ActivationMacrophage Migration-Inhibitory FactorsMacrophagesMonocytesReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSynovial MembraneT-LymphocytesTumor Necrosis Factor-alphaConceptsMacrophage migration inhibitory factorFibroblast-like synoviocytesRA fibroblast-like synoviocytesEnzyme-linked immunosorbent assayRheumatoid arthritisMigration inhibitory factorTNFalpha releaseExpression of MIFIntracellular macrophage migration inhibitory factorInhibitory factorCultured RA fibroblast-like synoviocytesCytokine macrophage migration inhibitory factorCultured fibroblast-like synoviocytesTumor necrosis factor-alpha synthesisHuman RA synoviumRA synovial tissueNecrosis factor-alpha synthesisHuman autoimmune diseasesPotential therapeutic targetTranscription-polymerase chain reactionMessenger RNA expressionT cell activationMIF expressionRA patientsRA synovium
1998
Filarial Nematode Parasites Secrete a Homologue of the Human Cytokine Macrophage Migration Inhibitory Factor
Pastrana D, Raghavan N, FitzGerald P, Eisinger S, Metz C, Bucala R, Schleimer R, Bickel C, Scott A. Filarial Nematode Parasites Secrete a Homologue of the Human Cytokine Macrophage Migration Inhibitory Factor. Infection And Immunity 1998, 66: 5955-5963. PMID: 9826378, PMCID: PMC108754, DOI: 10.1128/iai.66.12.5955-5963.1998.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorCytokine macrophage migration inhibitory factorMonocytes/macrophagesMigration inhibitory factorHuman monocytes/macrophagesExcretory-secretory productsInhibitory factorProinflammatory cytokine macrophage migration inhibitory factorParasite excretory-secretory productsMurine macrophage migration inhibitory factorLong-term chronic infectionsMonocyte/macrophage migrationHost immune responseHuman macrophage migration inhibitory factorFilarial nematode parasitesTh2 responsesTh2 biasAntiparasite immunityChronic infectionImmunological environmentFilarial antigenImmune responseUterine wallCytokine homologuesMacrophage migrationLocal Regulation of Macrophage Subsets in the Adult Rat Testis: Examination of the Roles of the Seminiferous Tubules, Testosterone, and Macrophage-Migration Inhibitory Factor1
Meinhardt A, Bacher M, Metz C, Bucala R, Wreford N, Lan H, Atkins R, Hedger M. Local Regulation of Macrophage Subsets in the Adult Rat Testis: Examination of the Roles of the Seminiferous Tubules, Testosterone, and Macrophage-Migration Inhibitory Factor1. Biology Of Reproduction 1998, 59: 371-378. PMID: 9687310, DOI: 10.1095/biolreprod59.2.371.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorSeminiferous tubule functionLeydig cell functionAdult rat testisMacrophage subsetsMacrophage numbersT implantsTubule functionAbdominal testesRat testisLeydig cellsResident macrophagesCytokine macrophage migration inhibitory factorMonocyte/macrophage subsetsCell functionMacrophage surface antigensResident macrophage numbersMacrophage migration inhibitoryMonoclonal antibody ED2MIF levelsLack of expressionSurface antigenInhibitory factorTestosterone implantsScrotal testesRegulation of the immune response by macrophage migration inhibitory factor: biological and structural features
Bernhagen J, Calandra T, Bucala R. Regulation of the immune response by macrophage migration inhibitory factor: biological and structural features. Journal Of Molecular Medicine 1998, 76: 151-161. PMID: 9535548, DOI: 10.1007/s001090050204.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorMigration inhibitory factorInhibitory factorCytokine macrophage migration inhibitory factorDelayed-type hypersensitivity reactionNegative septic shockB cell responsesMIF productionSeptic shockImmunosuppressive effectsHypersensitivity reactionsImmune responseImmunological functionsCell responsesHost macrophagesCritical mediatorGlucocorticoidsMediatorsBiological roleResponseCytokine structureCytokinesDiseaseMacrophagesStress response
1996
Delayed‐type hypersensitivity mediates Bowman's capsule rupture in Tamm—Horsfall protein‐induced tubulointerstitial nephritis in the rat
Qing S, NIKOLIC‐PATERSON D, ATKINS R, BACHER M, BUCALA R, Hui Y. Delayed‐type hypersensitivity mediates Bowman's capsule rupture in Tamm—Horsfall protein‐induced tubulointerstitial nephritis in the rat. Nephrology 1996, 2: 417-427. DOI: 10.1111/j.1440-1797.1996.tb00123.x.Peer-Reviewed Original ResearchBowman's capsule ruptureTamm-Horsfall proteinCapsule ruptureBowman's capsuleT cellsCapsule integrityTubulointerstitial nephritisWeek 26Immune responseSkin delayed-type hypersensitivity responseDelayed-type hypersensitivity responseCytokine macrophage migration inhibitory factorMacrophage migration inhibitory factorIntercellular adhesion molecule-1Interstitial T cellsDelayed-type hypersensitivityCellular immune responsesHumoral immune responseMigration inhibitory factorAdhesion molecule-1Site of ruptureIntact Bowman's capsuleRat crescentic glomerulonephritisGroups of animalsMacrophage-like cells
1994
Macrophage migration inhibitory factor is a neuroendocrine mediator of endotoxaemia
Bernhagen J, Calandra T, Cerami A, Bucala R. Macrophage migration inhibitory factor is a neuroendocrine mediator of endotoxaemia. Trends In Microbiology 1994, 2: 198-201. PMID: 8087451, DOI: 10.1016/0966-842x(94)90111-h.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorMigration inhibitory factorInhibitory factorCytokine macrophage migration inhibitory factorDelayed-type hypersensitivity reactionSystemic inflammatory responseIdentification of MIFT-cell productsCentral nervous systemAnterior pituitary glandHypersensitivity reactionsNeuroendocrine mediatorsInflammatory responseNervous systemPituitary glandCell productsEndotoxaemiaMajor protein constituentPituitaryHormoneProtein constituents