Featured Publications
Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity
Ruff WE, Dehner C, Kim WJ, Pagovich O, Aguiar CL, Yu AT, Roth AS, Vieira SM, Kriegel C, Adeniyi O, Mulla MJ, Abrahams VM, Kwok WW, Nussinov R, Erkan D, Goodman AL, Kriegel MA. Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity. Cell Host & Microbe 2019, 26: 100-113.e8. PMID: 31227334, PMCID: PMC8194364, DOI: 10.1016/j.chom.2019.05.003.Peer-Reviewed Original ResearchConceptsAntiphospholipid syndromePathogenic monoclonal antibodyHuman autoimmune diseasesGut commensalsB-cell autoepitopesHuman gut commensalGPI IgGAPS patientsIgG titersOral gavageMemory TSusceptible miceAntigenic loadAutoimmune diseasesAutoimmune pathologyTrigger autoimmunityHuman autoimmunityGlycoprotein IGPI autoantibodiesAutoimmunityMonoclonal antibodiesCell clonesCross reactMimotopesAutoantibodiesCommensal 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 commensals
2024
Lupus and inflammatory bowel disease share a common set of microbiome features distinct from other autoimmune disorders.
Zhou H, Balint D, Shi Q, Vartanian T, Kriegel M, Brito I. Lupus and inflammatory bowel disease share a common set of microbiome features distinct from other autoimmune disorders. Annals Of The Rheumatic Diseases 2024, ard-2024-225829. PMID: 39299726, DOI: 10.1136/ard-2024-225829.Peer-Reviewed Original ResearchProtein-protein interaction analysisMicrobial signaturesMicrobial profilesEffector-like proteinsSignaling pathwayInterleukin-12 signaling pathwayDisease mechanismsBacteria-derived proteinsMetagenomic datasetsMicrobiome featuresMicrobial underpinningsFunctional genesMicrobial biomarkersInteraction analysisMicrobial influenceInflammatory bowel diseaseMicrobial mechanismsGlucocorticoid signalingProteinGlucocorticoid receptorCritical roleAutoimmune diseasesPathwayBowel diseasePotential importance
2022
Subdoligranulum chews up joints: how a gut pathobiont can instigate arthritis
Kriegel M. Subdoligranulum chews up joints: how a gut pathobiont can instigate arthritis. Trends In Immunology 2022, 44: 4-6. PMID: 36494272, DOI: 10.1016/j.it.2022.11.006.Commentaries, Editorials and LettersConceptsRheumatoid arthritisSystemic autoimmune responseCertain autoimmune diseasesGnotobiotic mouse modelGut pathobiontSynovial inflammationAutoimmune responseAutoimmune diseasesMouse modelMonoclonal autoantibodiesArthritisGut commensalsHuman gut commensalAutoantibodiesOrigin hypothesisInflammationPathobiontsDiseaseSubdoligranulumEvolving concepts of host–pathobiont interactions in autoimmunity
Pereira M, Kriegel M. Evolving concepts of host–pathobiont interactions in autoimmunity. Current Opinion In Immunology 2022, 80: 102265. PMID: 36444784, DOI: 10.1016/j.coi.2022.102265.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAutoimmune diseasesSecondary lymphoid tissuesUnconventional therapeutic approachesAutoimmune pathwaysMucosal sitesLymphoid tissueMultistep pathogenesisTherapeutic approachesImmune functionMultifactorial diseaseDiseasePathobiontsSecretion of metabolitesNon-gut tissuesHuman microbiomeTissueAutoimmunityAutoantigensPathogenesisEnvironmental factorsSecretion
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 modelAutoimmunityPathobiontsMiceLymphocytesPrevention of systemic autoimmunity by dietary modulation of the gut microbiota
Ruiz D, El-Beidaq A, Iniguez A, di Ricco M, Mubiro D, Vieira S, Ruff W, Sterpka J, Kriegel M. Prevention of systemic autoimmunity by dietary modulation of the gut microbiota. The Journal Of Immunology 2018, 200: 54.1-54.1. DOI: 10.4049/jimmunol.200.supp.54.1.Peer-Reviewed Original ResearchSystemic lupus erythematosusType I interferonShort-chain fatty acidsI interferonB6 miceTg miceAutoimmune diseasesGut microbiotaHuman systemic lupus erythematosusDendritic cell accumulationImmune-microbiota interactionsPrototypical autoimmune diseaseOnset of diseaseAmeliorate autoimmunityLupus inductionLupus manifestationsKidney involvementLupus pathogenesisLupus erythematosusTLR7 agonistSystemic autoimmunityPeyer's patchesDietary modulationCell accumulationGut microbial community
2017
Commensal 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
2015
Autoimmune host–microbiota interactions at barrier sites and beyond
Ruff WE, Kriegel MA. Autoimmune host–microbiota interactions at barrier sites and beyond. Trends In Molecular Medicine 2015, 21: 233-244. PMID: 25771098, PMCID: PMC5918312, DOI: 10.1016/j.molmed.2015.02.006.Peer-Reviewed Original ResearchConceptsBarrier sitesAutoimmune animal modelsPathogenesis of autoimmunityBystander activationHost-microbiota interactionsAutoimmune diseasesAdaptive immunityAnimal modelsInfectious agentsAutoimmunityGnotobiotic approachesHomeostatic conditionsInternal organsCurrent literatureMicrobiotaDetrimental effectsHuman microbiome studiesDysbiosisPathogenesisMicrobiome studiesDiseaseImmunity
2014
Diet, microbiota and autoimmune diseases
Vieira S, Pagovich O, Kriegel M. Diet, microbiota and autoimmune diseases. Lupus 2014, 23: 518-526. PMID: 24763536, PMCID: PMC4009622, DOI: 10.1177/0961203313501401.Peer-Reviewed Original ResearchConceptsAutoimmune diseasesGut microbial communityGerm-free mouse modelDevelopment of autoimmunityDiet-derived metabolitesType 1 diabetesSeverity of diseaseLife-prolonging effectAdaptive immune systemAntiphospholipid syndromeAutoimmune modelSystemic lupusMultiple sclerosisGastrointestinal tractMurine modelMouse modelRodent modelsImmunomodulatory potentialCommensal bacteriaImmune systemCaloric restrictionGut microbiomeDietary changesLupusGut commensals
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