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
2025
An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis
El Bounkari O, Zan C, Yang B, Ebert S, Wagner J, Bugar E, Kramer N, Bourilhon P, Kontos C, Zarwel M, Sinitski D, Milic J, Jansen Y, Kempf W, Sachs N, Maegdefessel L, Ji H, Gokce O, Riols F, Haid M, Gerra S, Hoffmann A, Brandhofer M, Avdic M, Bucala R, Megens R, Willemsen N, Messerer D, Schulz C, Bartelt A, Harm T, Rath D, Döring Y, Gawaz M, Weber C, Kapurniotu A, Bernhagen J. An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis. Nature Communications 2025, 16: 2297. PMID: 40055309, DOI: 10.1038/s41467-025-57540-z.Peer-Reviewed Original ResearchConceptsApoE-/- miceHyperlipidemic apoE-/- miceCoronary artery diseaseDecreased plasma lipid levelsPlasma lipid levelsHepatic lipid accumulationAtherogenic chemokinesFoam-cell formationFLIM-FRET microscopyArtery diseasePlasma concentrationsVascular inflammationInflammatory conditionsMetabolic dysfunctionAtherosclerotic patientsLipid accumulationAdvanced atherosclerosisMyocardial infarctionLipid levelsSuppressed hepatic lipid accumulationAdvanced atherogenesisCarotid plaquesDisease severityIschemic strokeChemokinesDistinctive Macrophage Migration Inhibitory Factor Receptor Patterns and Soluble Biomarkers in Rheumatoid Arthritis: Unveiling Key Associations with Disease Activity
SĂĄnchez-Zuno G, Bucala R, HernĂĄndez-Bello J, Palafox-SĂĄnchez C, VizcaĂno-Quirarte A, Muñoz-Valle J. Distinctive Macrophage Migration Inhibitory Factor Receptor Patterns and Soluble Biomarkers in Rheumatoid Arthritis: Unveiling Key Associations with Disease Activity. Journal Of Interferon & Cytokine Research 2025, 45: 99-106. PMID: 39914814, DOI: 10.1089/jir.2024.0184.Peer-Reviewed Original ResearchConceptsMigration inhibitory factorMigration inhibitory factor levelsDisease activityRA patientsControl subjectsRheumatoid arthritisLevels of migration inhibitory factorSerum levels of CXCL12Levels of CXCL12Serum of RA patientsModerate disease activityMembranous expression patternRheumatoid factor titerMIF levelsCXCL12 levelsSerum levelsCXCL8 levelsSoluble biomarkersTreatment protocolsPattern of expressionSerum CXCL8PatientsReceptor patternsClinical biomarkersInhibitory factorDecreased T helper 1 cell function underlies recurrent sinopulmonary infections in the 17q12 deletion syndrome
Shin J, Shin H, Gutierrez A, Yoo N, Par-Young J, Osmani L, Shin M, Sanchez-Lara P, Bucala R, Soffer G, Kang I. Decreased T helper 1 cell function underlies recurrent sinopulmonary infections in the 17q12 deletion syndrome. EBioMedicine 2025, 112: 105578. PMID: 39891996, PMCID: PMC11840234, DOI: 10.1016/j.ebiom.2025.105578.Peer-Reviewed Original ResearchConceptsCD4<sup>+</sup> T cellsRecurrent sinopulmonary infectionsT cell functionRNA-seq analysisT cellsHealthy controlsSinopulmonary infectionsRNA-seqT-betIFN-gFrequency of CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cell functionTh1 transcription factor T-betDeletion syndromeFlow cytometryCompared to age-matched healthy controlsTranscription factor T-betDecreased T-betUrinary tract abnormalitiesAge-matched healthy controlsMultiplex assayDownstream effector cytokinesEffector cytokinesRecurrent infectionsTh17 cytokines
2024
Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma
Valdez C, SĂĄnchez-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, SĂĄnchez-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 ProblemâBased Immunology Review Series With Great Educational Potential
Bucala R, Solomon D. Immunology for the Rheumatologist: Arthritis & Rheumatology Introduces a New ProblemâBased 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 Sjögrenâs 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 Sjögrenâs 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-1ÎČIL-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 profileâNear Cureâ 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. âNear Cureâ 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: âMidâTermâ Report
Solomon DH, Bucala R, Kaplan MJ, Nigrovic PA. Arthritis & Rheumatology: âMidâTermâ Report. Arthritis & Rheumatology 2022, 74: 1099-1101. PMID: 35358367, DOI: 10.1002/art.42131.Peer-Reviewed Original ResearchManaging COVID-19 going forwardâthe lessons from history
Bucala R, Friedland G, Snowden F. Managing COVID-19 going forwardâthe lessons from history. QJM 2022, 115: 649-650. PMID: 35262710, PMCID: PMC9383561, DOI: 10.1093/qjmed/hcac065.Peer-Reviewed Original Research
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