Featured Publications
MIF is a common genetic determinant of COVID-19 symptomatic infection and severity
Shin JJ, Fan W, Par-Young J, Piecychna M, Leng L, Israni-Winger K, Qing H, Gu J, Zhao H, Schulz WL, Unlu S, Kuster J, Young G, Liu J, Ko AI, Garcia A, Sauler M, Wisnewski AV, Young L, Orduña A, Wang A, Klementina O, Garcia AB, Hegyi P, Armstrong ME, Mitchell P, Ordiz DB, Garami A, Kang I, Bucala R. MIF is a common genetic determinant of COVID-19 symptomatic infection and severity. QJM 2022, 116: 205-212. PMID: 36222594, PMCID: PMC9620729, DOI: 10.1093/qjmed/hcac234.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorLow-expression MIF alleleCOVID-19 infectionMIF allelesCATT7 alleleHealthy controlsCOVID-19Serum macrophage migration inhibitory factorSymptomatic SARS-CoV-2 infectionHigher serum MIF levelsHigh-expression MIF allelesRetrospective case-control studySARS-CoV-2 infectionFunctional polymorphismsAvailable clinical characteristicsMultinational retrospective studySerum MIF levelsUninfected healthy controlsSymptomatic COVID-19Tertiary medical centerHealthy control subjectsCase-control studyMigration inhibitory factorCoronavirus disease 2019Common functional polymorphisms
2024
Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma
Valdez C, Sánchez-Zuno G, Osmani L, Ibrahim W, Galan A, Bacchiocchi A, Halaban R, Kulkarni R, Kang I, Bucala R, Tran T. Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma. Oncotarget 2024, 15: 507-520. PMID: 39028303, PMCID: PMC11259151, DOI: 10.18632/oncotarget.28615.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigens, Differentiation, B-LymphocyteBiomarkers, TumorFemaleHistocompatibility Antigens Class IIHumansImmune Checkpoint InhibitorsIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMaleMelanomaMiddle AgedMutationPrognosisRetrospective StudiesSkin NeoplasmsConceptsMacrophage migration inhibitory factorImmune checkpoint inhibitionD-dopachrome tautomeraseExpression of macrophage migration inhibitory factorDrivers of tumor progressionInflammatory cell markersPatient tumor samplesPatient survival outcomesMigration inhibitory factorStatistically significant differenceCheckpoint inhibitionImmune therapyPrognostic valueSurvival outcomesResistant melanomaGene expressionImproved survivalRetrospective studyInflammatory markersTumor progressionCell markersTumor samplesClinical evidenceMelanomaBulk RNA sequencingDownregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia
Huang Y, Chen L, Li L, Qi Y, Tong H, Wu H, Xu J, Leng L, Cheema S, Sun G, Xia Z, McGuire J, Rodrigues B, Young L, Bucala R, Qi D. Downregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia. JCI Insight 2024, 9: e173240. PMID: 38973609, PMCID: PMC11383372, DOI: 10.1172/jci.insight.173240.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorDevelopment of hypertriglyceridemiaWhite adipose tissueAdipose LPLPAR2 expressionLevels of macrophage migration inhibitory factorElevated plasma TG levelsLPL expressionLipoprotein lipaseIncrease PAR2 expressionPlasma MIF levelsPlasma TG levelsMigration inhibitory factorPalmitic acid dietInhibited Akt phosphorylationMIF levelsLipoprotein lipase geneTG levelsObese humansPlasma TGHypertriglyceridemiaAkt phosphorylationLipid storageInhibitory factorAdipose tissueMacrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities
Valdez C, Sánchez-Zuno G, Bucala R, Tran T. Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities. International Journal Of Molecular Sciences 2024, 25: 4849. PMID: 38732068, PMCID: PMC11084905, DOI: 10.3390/ijms25094849.Peer-Reviewed Original ResearchConceptsInhibition of MIFResponse to infectionNon-canonical signaling pathwaysClinical studiesCancer patientsClinical trialsInflammatory cytokinesDriving tumorigenesisClinical explorationCancer typesCancerDual inhibitionTherapeutic targetIn vivoIn vitroSignaling pathwayMIFAntitumor candidateBinding partnersIL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination
Park H, Shin M, Shin J, Kim H, Kang B, Par-Young J, Unlu S, Afinogenova Y, Catanzaro J, Young J, Kim M, Lee S, Jeon S, You S, Racke M, Bucala R, Kang I. IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination. EBioMedicine 2024, 103: 105114. PMID: 38640835, PMCID: PMC11041015, DOI: 10.1016/j.ebiom.2024.105114.Peer-Reviewed Original ResearchConceptsCD4<sup>+</sup> T cellsCOVID-19 mRNA vaccinesAntigen-specific CD4<sup>+</sup> T cell responsesT cell responsesPrimary antibody deficiencyCD4<sup>+</sup> T cell responsesT cellsIL-1R1MRNA vaccinesIL-1IgG antibodiesAntigen-specific CD4<sup>+</sup> T cellsCD4+ T cell responsesLevels of IL-1R1Human CD4<sup>+</sup> T cellsIL-1 receptor 1Healthy individualsDose of COVID-19 mRNA vaccineAntigen-specific CD4IL-1R1 expressionT cell immunityRepetitive antigenic stimulationCytokines interleukin (IL)-1Immune response to virusesExpression of IL-1R1MIF contribution to progressive brain diseases
Matejuk A, Benedek G, Bucala R, Matejuk S, Offner H, Vandenbark A. MIF contribution to progressive brain diseases. Journal Of Neuroinflammation 2024, 21: 8. PMID: 38178143, PMCID: PMC10765708, DOI: 10.1186/s12974-023-02993-6.Peer-Reviewed Original ResearchConceptsBrain diseasesMultiple sclerosisAlzheimer's diseaseMacrophage migration inhibitory factorModulation of neuroinflammationNumerous neurologic diseasesMigration inhibitory factorProgressive brain diseaseNew therapeutic strategiesInflammatory mediatorsChronic inflammationAutoimmune diseasesVascular diseaseNervous system developmentNeurologic diseaseNeuroendocrine functionPsychiatric disordersTherapeutic strategiesEconomic burdenNeurological diseasesNew biomarkersInhibitory factorNeurodegenerative pathologiesDiseaseNovel therapeuticsPotential role of RhoA GTPase regulation in type interferon signaling in systemic lupus erythematosus
Fan W, Wei B, Chen X, Zhang Y, Xiao P, Li K, Zhang Y, Huang J, Leng L, Bucala R. Potential role of RhoA GTPase regulation in type interferon signaling in systemic lupus erythematosus. Arthritis Research & Therapy 2024, 26: 31. PMID: 38243295, PMCID: PMC10799493, DOI: 10.1186/s13075-024-03263-3.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsRhoA GTPaseExpression levelsTreatment of SLEFunctions of RhoA.Knockdown of RhoAI IFN-stimulated genesSiRNA-mediated knockdownI interferonEnzyme-linked immunoassayIFN-stimulated genesGTPase signalingExpression levels of RhoASLE patientsLevels of RhoALupus erythematosusSLE peripheral blood mononuclear cellsGTPase regulatorHealthy controlsExpression of RhoAResponse pathwaysReporter gene assayRhoAType I IFN signalingSignal transducer
2023
Immunology for the Rheumatologist: Arthritis & Rheumatology Introduces a New Problem‐Based Immunology Review Series With Great Educational Potential
Bucala R, Solomon D. Immunology for the Rheumatologist: Arthritis & Rheumatology Introduces a New Problem‐Based Immunology Review Series With Great Educational Potential. Arthritis & Rheumatology 2023, 76: 9-10. PMID: 37655656, DOI: 10.1002/art.42688.Peer-Reviewed Original ResearchThe 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 SNPsGlioblastomaReflections for the 50th Anniversary of The Journal of Rheumatology: The Past, Present, and Future of Rheumatology
Masi A, Bucala R. Reflections for the 50th Anniversary of The Journal of Rheumatology: The Past, Present, and Future of Rheumatology. The Journal Of Rheumatology 2023, 50: 144-146. PMID: 36587952, DOI: 10.3899/jrheum.220588.Peer-Reviewed Original Research
2022
Clinical features and high-risk indicators of central nervous system involvement in primary Sjögren’s syndrome
Fan W, Par-Young J, Li K, Zhang Y, Xiao P, Hua L, Leng L, Chen X, Bucala R. Clinical features and high-risk indicators of central nervous system involvement in primary Sjögren’s syndrome. Clinical Rheumatology 2022, 42: 443-451. PMID: 36401063, PMCID: PMC9873757, DOI: 10.1007/s10067-022-06448-w.Peer-Reviewed Original ResearchConceptsCentral nervous system involvementNervous system involvementPotential risk factorsPrimary Sjögren's syndrome patientsHigh-dose glucocorticoidsSjögren's syndrome patientsCNS involvementSystem involvementHigh-risk indicatorsImmunosuppressive therapyLung involvementSyndrome patientsC3 levelsRisk factorsPulmonary involvementPS patientsHigh-dose glucocorticoid administrationMultivariate logistic regression analysisAnti-SSA positivityHigh titer ANAAnti-SSA antibodiesLow C3 levelsPrimary Sjögren's syndromeComplement 4 levelsLogistic regression analysisCD74 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 cellsTranscriptionGenesMacrophage Migration Inhibitory Factor (MIF) Promotes Increased Proportions of the Highly Permissive Th17-like Cell Profile during HIV Infection
Trifone C, Baquero L, Czernikier A, Benencio P, Leng L, Laufer N, Quiroga MF, Bucala R, Ghiglione Y, Turk G. Macrophage Migration Inhibitory Factor (MIF) Promotes Increased Proportions of the Highly Permissive Th17-like Cell Profile during HIV Infection. Viruses 2022, 14: 2218. PMID: 36298774, PMCID: PMC9611675, DOI: 10.3390/v14102218.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorMIF stimulationMIF treatmentIL-17AHIV infectionMIF/CD74 axisFounder HIV-1Functionality of CD4Higher IL-17AHigher MIF concentrationsMIF plasma levelsHIV-1 infectionMigration inhibitory factorPossible therapeutic targetMIF concentrationsIntracellular cytokinesR5-tropicCytokine productionIL-1βIL-6IL-8Plasma levelsHealthy donorsViral persistenceT lymphocytesDefining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency
Shin JJ, Par-Young J, Unlu S, McNamara A, Park HJ, Shin MS, Gee RJ, Doyle H, Afinogenova Y, Zidan E, Kwah J, Russo A, Mamula M, Hsu FI, Catanzaro J, Racke M, Bucala R, Wilen C, Kang I. Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency. Journal Of Clinical Immunology 2022, 42: 1137-1150. PMID: 35713752, PMCID: PMC9203263, DOI: 10.1007/s10875-022-01296-4.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, ViralCD8-Positive T-LymphocytesCommon Variable ImmunodeficiencyCOVID-19COVID-19 VaccinesHumansImmunity, CellularImmunoglobulin AImmunoglobulin GMRNA VaccinesPrimary Immunodeficiency DiseasesRNA, MessengerSARS-CoV-2Spike Glycoprotein, CoronavirusVaccinationVaccinesVaccines, SyntheticConceptsCommon variable immune deficiencyT cellsImmune responseIgG responsesCVID patientsMRNA vaccinesB cellsCoronavirus disease 2019 (COVID-19) mRNA vaccinesCOVID-19 mRNA vaccinesBaseline immune profileHistory of autoimmunityPrimary antibody deficiencyT cell responsesCellular immune responsesPoor immune responseVariable immune deficiencyMemory B cellsSARS-CoV-2 spike proteinBaseline IgGCVID diagnosisEM CD8Immunological predictorsPAD cohortSpecific CD4Immune profile“Near Cure” treatment of severe acute EAE in MIF-1-deficient female and male mice with a bifunctional MHCII-derived molecular construct
Vandenbark AA, Meza-Romero R, Wiedrick J, Gerstner G, Seifert H, Kent G, Piechycna M, Benedek G, Bucala R, Offner H. “Near Cure” treatment of severe acute EAE in MIF-1-deficient female and male mice with a bifunctional MHCII-derived molecular construct. Cellular Immunology 2022, 378: 104561. PMID: 35738135, PMCID: PMC9714992, DOI: 10.1016/j.cellimm.2022.104561.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisAcute experimental autoimmune encephalomyelitisDRα1-MOG-35Multiple sclerosisMIF-1EAE scoresMale miceMIF-2Severe diseaseMacrophage migration inhibitory factorClinical EAE scoresMIF-deficient micePeripheral inflammatory cellsMigration inhibitory factorSpinal cord tissueT cell activationSex-dependent differencesEAE severityAutoimmune encephalomyelitisSerum levelsTreatment of WTInflammatory cellsFemale miceClinical signsCord tissueArthritis & Rheumatology: “Mid‐Term” Report
Solomon DH, Bucala R, Kaplan MJ, Nigrovic PA. Arthritis & Rheumatology: “Mid‐Term” Report. Arthritis & Rheumatology 2022, 74: 1099-1101. PMID: 35358367, DOI: 10.1002/art.42131.Peer-Reviewed Original ResearchManaging COVID-19 going forward—the lessons from history
Bucala R, Friedland G, Snowden F. Managing COVID-19 going forward—the lessons from history. QJM 2022, 115: 649-650. PMID: 35262710, PMCID: PMC9383561, DOI: 10.1093/qjmed/hcac065.Peer-Reviewed Original ResearchInterleukin-17 Contributes to Chikungunya Virus-Induced Disease
Liu X, Poo YS, Alves JC, Almeida RP, Mostafavi H, Tang PCH, Bucala R, Teixeira MM, Taylor A, Zaid A, Mahalingam S. Interleukin-17 Contributes to Chikungunya Virus-Induced Disease. MBio 2022, 13: e00289-22. PMID: 35254128, PMCID: PMC9040832, DOI: 10.1128/mbio.00289-22.Peer-Reviewed Original ResearchConceptsIL-17Chikungunya virusCHIKV infectionRheumatoid arthritisIL-17A-deficient miceIL-17-deficient miceInterleukin-17 ContributesSpecific antiviral drugsWild-type miceIL-17 signalingAlphaviral arthritidesIL-17AIL-23Neutrophil infiltrationPsoriatic arthritisArthritic inflammationIL-21Acute phaseIL-22Interleukin-17Chronic phaseIL-6Tissue infiltratesTissue inflammationDisease patientsCD74 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
Global Rheumatology Research: Frontiers, Challenges, and Opportunities
Bilsborrow JB, Peláez‐Ballestas I, Pons‐Estel B, Scott C, Tian X, Alarcon GS, Bucala R, Lewandowski LB, Hsieh E. Global Rheumatology Research: Frontiers, Challenges, and Opportunities. Arthritis & Rheumatology 2021, 74: 1-4. PMID: 34535973, PMCID: PMC8712358, DOI: 10.1002/art.41980.Books