Featured Publications
Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus
Greiling TM, Dehner C, Chen X, Hughes K, Iñiguez AJ, Boccitto M, Ruiz DZ, Renfroe SC, Vieira SM, Ruff WE, Sim S, Kriegel C, Glanternik J, Chen X, Girardi M, Degnan P, Costenbader KH, Goodman AL, Wolin SL, Kriegel MA. Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus. Science Translational Medicine 2018, 10 PMID: 29593104, PMCID: PMC5918293, DOI: 10.1126/scitranslmed.aan2306.Peer-Reviewed Original ResearchConceptsLupus patientsGlomerular immune complex depositsPositive lupus patientsImmune complex depositsGerm-free miceSigns of autoimmunityB cell responsesT cell clonesNovel treatment approachesTriggers of autoimmunityCommensal bacterial speciesEarliest autoantibodiesChronic autoimmunityAutoimmune diseasesHealthy controlsT cellsTreatment approachesSusceptible individualsAutoimmunityCell responsesCommensal speciesLupusPatientsCell clonesGut commensalsTranslocation of a gut pathobiont drives autoimmunity in mice and humans
Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, Costa FRC, Tiniakou E, Greiling T, Ruff W, Barbieri A, Kriegel C, Mehta SS, Knight JR, Jain D, Goodman AL, Kriegel MA. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science 2018, 359: 1156-1161. PMID: 29590047, PMCID: PMC5959731, DOI: 10.1126/science.aar7201.Peer-Reviewed Original ResearchConceptsGut pathobiontAutoimmune-prone miceMurine findingsIntramuscular vaccinePathogenic autoantibodiesLiver biopsyAutoimmune responseAutoimmune patientsAntibiotic treatmentT cellsImmune diseasesAutoimmunitySusceptible humansPathobiontsSystemic tissuesHuman hepatocytesAutoantibodiesMortalityMiceCocultureHepatocytesGenetic backgroundTissueBiopsyPatients
2018
Gut pathobiont translocation induces lymphocyte migration to internal organs in autoimmunity
Fine R, Vieira S, Ruiz D, Kriegel M. Gut pathobiont translocation induces lymphocyte migration to internal organs in autoimmunity. The Journal Of Immunology 2018, 200: 102.16-102.16. DOI: 10.4049/jimmunol.200.supp.102.16.Peer-Reviewed Original ResearchC57BL/6 miceT cellsLymphocyte migrationInternal organsE. gallinarumProne C57BL/6 miceSystemic autoimmune diseaseSecondary lymphoid organsAutoimmune-prone (NZB/NZW) F1 miceGut homingGut pathobiontOral antibioticsSplenic CD4Autoantibody productionHost-microbiota interactionsAutoimmune diseasesSystemic autoimmunityLymphoid organsPeyer's patchesF1 miceMouse modelAutoimmunityPathobiontsMiceLymphocytesGut commensal-dependent production of autoantibodies against the primordial lupus autoantigen Ro60 in the absence of mammalian Ro60.
Datta R, Dehner C, Ruff W, Greiling T, Kriegel M. Gut commensal-dependent production of autoantibodies against the primordial lupus autoantigen Ro60 in the absence of mammalian Ro60. The Journal Of Immunology 2018, 200: 162.11-162.11. DOI: 10.4049/jimmunol.200.supp.162.11.Peer-Reviewed Original ResearchAnti-Ro60 autoantibodiesSystemic lupus erythematosusB6 miceGut microbiotaSLE-like diseaseTraditional risk factorsDevelopment of lupusBroad-spectrum antibioticsMurine gut microbiotaLupus erythematosusAntigenic triggerAutoimmune responseTg miceInterventional studyKO miceRisk factorsIgG ELISAAutoantibody inductionDisease manifestationsOral administrationT cellsAutoantibodiesMiceRo60LupusSkin Microbiota as Antigenic Triggers for Cutaneous T Cell Lymphoma
Dehner C, Ruff W, Foss F, Girardi M, Kriegel M. Skin Microbiota as Antigenic Triggers for Cutaneous T Cell Lymphoma. The Journal Of Immunology 2018, 200: 166.24-166.24. DOI: 10.4049/jimmunol.200.supp.166.24.Peer-Reviewed Original ResearchCutaneous T-cell lymphomaT-cell lymphomaT cellsSkin lesionsCell lymphomaPathogenesis of CTCLActive skin lesionsCutaneous T-cellChronic skin lesionsAdaptive immune responsesPatient T cellsSLE patientsCTCL patientsAntigenic triggerLesional skinRRNA sequencingAntigenic challengeMALT lymphomaHealthy donorsImmune responseAntigenic driversSkin commensalsPatient biopsiesClonal proliferationV1-3
2017
Autoantigen‐specific T and B Cell Cross‐reactivity to a Gut Commensal in Antiphospholipid Syndrome
Dehner C, Ruff W, Vieira S, Goodman A, Kriegel M. Autoantigen‐specific T and B Cell Cross‐reactivity to a Gut Commensal in Antiphospholipid Syndrome. The FASEB Journal 2017, 31 DOI: 10.1096/fasebj.31.1_supplement.184.7.Peer-Reviewed Original ResearchBALB/c miceAdaptive immune systemAntiphospholipid syndromeB cellsC miceT cellsCell epitopesImmune systemPathogenic T cell epitopesTetramer-positive T cellsCD4 memory T cellsMemory T cellsTNF-α ILAdaptive immune responsesT cell clonesT cell epitopesDose-responsive mannerHuman commensal bacteriumB-cell epitopesEpitope-specific monoclonal antibodiesIL-21Patient PBMCsLymph nodesGPI antibodiesAntigenic challengeCommensal Ro60 Orthologs as Persistent Triggers of Human Lupus
Dehner C, Greiling T, Chen X, Renfroe S, Hughes K, Vieira S, Ruff W, Boccitto M, Sim S, Chen X, Kriegel C, Degnan P, Goodman A, Wolin S, Kriegel M. Commensal Ro60 Orthologs as Persistent Triggers of Human Lupus. The FASEB Journal 2017, 31 DOI: 10.1096/fasebj.31.1_supplement.55.3.Peer-Reviewed Original ResearchMesenteric lymph nodesSystemic lupus erythematosusT cell clonesLupus patientsSLE patientsTg miceAutoimmune diseasesMicrobial triggersCell clonesT cellsGerm-free (GF) C57BL/6 miceP. propionicumMemory CD4 T cellsHuman SLE seraPrototypical autoimmune diseaseCD4 T cellsHuman autoimmune diseasesGerm-free miceAnti-Ro60 antibodiesEarliest autoantibodiesRo60 antibodiesLupus modelsLupus erythematosusLymph nodesHuman lupus
2016
Lupus T and B cell cross-reactivity between the human Ro60 autoantigen and Ro60 orthologs from the human microbiota
Greiling T, Dehner C, Renfroe S, Chen X, Vieira S, Ruff W, Goodman A, Wolin S, Kriegel M. Lupus T and B cell cross-reactivity between the human Ro60 autoantigen and Ro60 orthologs from the human microbiota. The Journal Of Immunology 2016, 196: 124.16-124.16. DOI: 10.4049/jimmunol.196.supp.124.16.Peer-Reviewed Original ResearchLupus patientsAnti-Ro60 antibodiesB cellsP. propionicumGerm-free miceGut commensalsHuman lupus patientsHuman microbiotaT cell clonesNovel therapeutic approachesSubset of skinAutoimmune TEarliest autoantibodiesLupus TRo60 antibodiesIgA antibodiesChronic autoimmunityMemory TSystemic autoimmunityHealthy controlsT cellsTherapeutic approachesPatientsSusceptible individualsAutoimmunity
2015
A common gut commensal as a cross-reactive candidate in antiphospholipid syndrome (HUM3P.250)
Dehner C, Ruff W, VIEIRA S, Goodman A, Kriegel M. A common gut commensal as a cross-reactive candidate in antiphospholipid syndrome (HUM3P.250). The Journal Of Immunology 2015, 194: 121.10-121.10. DOI: 10.4049/jimmunol.194.supp.121.10.Peer-Reviewed Original ResearchAntiphospholipid syndromeGut commensalsCD4 memory T cellsB-cell immunodominant epitopesWestern blottingIL-17 secretionMemory T cellsB cell responsesAdaptive immune responsesCommon gut commensalPatient plasma samplesAPS patientsIL-10IL-2IL-4T cellsImmune responseImmunodominant epitopesGut microbiotaTh1 clonesMajor autoantigenMolecular mimicryCell responsesPlasma samplesAntigenic potential
2012
Pancreatic islet expression of chemokine CCL2 suppresses autoimmune diabetes via tolerogenic CD11c+ CD11b+ dendritic cells
Kriegel MA, Rathinam C, Flavell RA. Pancreatic islet expression of chemokine CCL2 suppresses autoimmune diabetes via tolerogenic CD11c+ CD11b+ dendritic cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 3457-3462. PMID: 22328150, PMCID: PMC3295274, DOI: 10.1073/pnas.1115308109.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoimmunityCD11b AntigenCD11c AntigenCD4-Positive T-LymphocytesCell CountChemokine CCL2Dendritic CellsDiabetes Mellitus, Type 1FemaleGene Expression RegulationInsulinIslets of LangerhansLymph NodesMiceMice, Inbred NODMice, TransgenicPromoter Regions, GeneticRatsRecombinant Fusion ProteinsSelf ToleranceConceptsDendritic cellsType 1 diabetesCell infiltrateDiabetes developmentT cellsChemokine CCL2/MCPElevated IL-10 secretionPancreatic isletsCCL2/CCR2 axisCD80/CD86 expressionTransgenic NOD miceVivo transfer systemDendritic cell biologyImmune cell infiltratesIL-10 secretionNonobese diabetic (NOD) miceCCL2/MCPRat insulin promoterUnexpected beneficial roleHypoactive phenotypeLow CD40NOD backgroundPancreatic lymphAutoimmune diabetesNOD mice
2011
Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice
Kriegel MA, Sefik E, Hill JA, Wu HJ, Benoist C, Mathis D. Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 11548-11553. PMID: 21709219, PMCID: PMC3136249, DOI: 10.1073/pnas.1108924108.Peer-Reviewed Original ResearchConceptsDiabetes protectionSFB colonizationSmall intestinal lamina propriaSystemic lymphoid tissuesExperimental autoimmune encephalomyelitisNonobese diabetic (NOD) miceT cell compartmentImmune system alterationsType 1 diabetesDifferent Th subsetsSegmented filamentous bacteriaHost physiological functionsNOD miceAutoimmune encephalomyelitisInflammatory arthritisTh17 cellsTh subsetsAutoimmune responseDiabetic miceLymphoid tissueSI-LPSpontaneous modelT cellsLamina propriaMouse model
2009
E3 ubiquitin ligase GRAIL controls primary T cell activation and oral tolerance
Kriegel MA, Rathinam C, Flavell RA. E3 ubiquitin ligase GRAIL controls primary T cell activation and oral tolerance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 16770-16775. PMID: 19805371, PMCID: PMC2757842, DOI: 10.1073/pnas.0908957106.Peer-Reviewed Original ResearchConceptsPrimary T cell activationOral toleranceT cellsT cell activationCell activationT helper 1 cellsAntigen-specific strategiesOrgan-specific autoimmunityExperimental allergic encephalitisT cell unresponsivenessElevated baseline levelsNaïve T cellsT cell anergySelf-reactive lymphocytesAnergic T cellsMechanism of actionMyelin basic proteinOral tolerizationSignificant hypersecretionMAP kinases ERK1/2Allergic encephalitisAnergic phenotypeCell unresponsivenessAnergic stateAutoimmune diseases
2004
Defective Suppressor Function of Human CD4+ CD25+ Regulatory T Cells in Autoimmune Polyglandular Syndrome Type II
Kriegel MA, Lohmann T, Gabler C, Blank N, Kalden JR, Lorenz HM. Defective Suppressor Function of Human CD4+ CD25+ Regulatory T Cells in Autoimmune Polyglandular Syndrome Type II. Journal Of Experimental Medicine 2004, 199: 1285-1291. PMID: 15117972, PMCID: PMC2211900, DOI: 10.1084/jem.20032158.Peer-Reviewed Original ResearchConceptsAutoimmune polyglandular syndromeRegulatory T cellsAPS IIT cellsAutoimmune polyglandular syndrome type IIOrgan-specific autoimmune diseasesAPS type IAPS type IIDefective suppressor functionNormal healthy donorsImportant surface markerPolyglandular syndromeAutoimmune endocrinopathiesControl patientsMultiple endocrinopathiesAutoimmune diseasesPeripheral bloodSuppressive capacityType IIHealthy donorsHuman autoimmunityCentral toleranceHuman CD4Murine modelSurface markers