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 reactMimotopesAutoantibodiesA Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity
Zegarra-Ruiz DF, Beidaq A, Iñiguez AJ, Di Ricco M, Vieira S, Ruff WE, Mubiru D, Fine RL, Sterpka J, Greiling TM, Dehner C, Kriegel MA. A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity. Cell Host & Microbe 2018, 25: 113-127.e6. PMID: 30581114, PMCID: PMC6377154, DOI: 10.1016/j.chom.2018.11.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoimmunityClostridiaceaeDendritic CellsDietDiet TherapyDisease Models, AnimalDNA, RibosomalFatty Acids, VolatileFecesFemaleGastrointestinal MicrobiomeGerm-Free LifeGlomerulonephritisHumansHypersensitivityInterferon Type IKidneyLactobacillusLimosilactobacillus reuteriLupus Erythematosus, SystemicMembrane GlycoproteinsMiceMice, Inbred C57BLRNA, Ribosomal, 16SStarchSurvival RateToll-Like Receptor 7ConceptsPlasmacytoid dendritic cellsSystemic lupus erythematosusInterferon pathwayToll-like receptor 7L. reuteri colonizationGut microbiota compositionDietary resistant starchShort-chain fatty acidsAutoimmune manifestationsDependent mouse modelSLE patientsOrgan involvementDendritic cellsLupus erythematosusReceptor 7Systemic autoimmunityHuman autoimmunityMouse modelGut microbiotaMetabolic diseasesMicrobiota compositionWestern lifestyleAutoimmunityDietary effectsBeneficial effectsCommensal 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
2022
Evolving 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
2021
Chapter 25 Microbiota influences on systemic lupus erythematosus and Sjögren’s syndrome
Greiling T, Vieira S, Kriegel M. Chapter 25 Microbiota influences on systemic lupus erythematosus and Sjögren’s syndrome. 2021, 211-221. DOI: 10.1016/b978-0-12-814551-7.00025-8.Peer-Reviewed Original ResearchSystemic lupus erythematosusSjögren's syndromeLupus erythematosusSystemic autoimmunityAdaptive immune responsesPathogenesis of autoimmunityToll-like receptorsProne hostsBarrier organsImmune responseAdaptive immunityInnate triggersAnimal modelsMicrobiota influenceCommensal bacteriaSyndromeMucus membranesAutoimmunityHuman autoantigensErythematosusPathogenesisMicrobiotaLive bacteriaHost tissuesInflammationChapter 9 Immunopathogenesis: the role of mucosal and skin microbiota in SLE
Greiling T, Kriegel M. Chapter 9 Immunopathogenesis: the role of mucosal and skin microbiota in SLE. 2021, 117-130. DOI: 10.1016/b978-0-12-820583-9.00012-9.Peer-Reviewed Original Research
2018
Spontaneous translocation of a human enterococcal gut pathobiont drives systemic autoimmunity
Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Barbieri A, Jain D, Goodman A, Kriegel M. Spontaneous translocation of a human enterococcal gut pathobiont drives systemic autoimmunity. The Journal Of Immunology 2018, 200: 162.10-162.10. DOI: 10.4049/jimmunol.200.supp.162.10.Peer-Reviewed Original ResearchHost-microbiota interactionsOral vancomycin treatmentInduction of autoantibodiesPlasmacytoid dendritic cellsMesenteric lymph nodesPathogenesis of autoimmunityE. gallinarumAutoimmune hepatitisTfh cellsLupus patientsOrgan manifestationsPathogenic autoantibodiesDendritic cellsLymph nodesCytokines IFNGut barrierVancomycin treatmentC57BL/6 animalsSystemic autoimmunityInduction of moleculesLiver tissueAutoimmunityAhR pathwayBarrier functionMucus layerGut 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 modelAutoimmunityPathobiontsMiceLymphocytes
2017
Spontaneous Translocation of a Gut Pathobiont Drives Autoimmunity that is Preventable by Intramuscular Vaccination
Vieira S, Hiltensperger M, Kumar V, Dehner C, Zegarra-Ruiz D, Ruff W, Khan N, Goodman A, Kriegel M. Spontaneous Translocation of a Gut Pathobiont Drives Autoimmunity that is Preventable by Intramuscular Vaccination. The Journal Of Immunology 2017, 198: 199.20-199.20. DOI: 10.4049/jimmunol.198.supp.199.20.Peer-Reviewed Original ResearchMesenteric lymph nodesGut microbiotaE. gallinarumGerm-free (GF) C57BL/6 miceAutoimmune hepatitis patientsInduction of autoantibodiesPathogenesis of autoimmunityNovel therapeutic avenuesTfh cellsDietary antigensIntramuscular vaccineIntramuscular vaccinationHepatitis patientsLymph nodesGut barrierHost-microbiota interactionsOral gavageC57BL/6 miceSystemic autoimmunityPortal veinTherapeutic avenuesAutoimmunitySingle antibioticLiver tissueMice
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
Gut commensal dependence of autoreactivity and Th17 cells in systemic autoimmunity (MUC9P.740)
Manfredo Vieira S, Ruff W, Hiltensperger M, Yu A, Goodman A, Kriegel M. Gut commensal dependence of autoreactivity and Th17 cells in systemic autoimmunity (MUC9P.740). The Journal Of Immunology 2015, 194: 205.4-205.4. DOI: 10.4049/jimmunol.194.supp.205.4.Peer-Reviewed Original ResearchAntiphospholipid syndromeSegmented filamentous bacteriaSystemic autoimmunityGut microbiotaAntiphospholipid antibody productionRegulatory IL-10Gut microbiota compositionAntigen-specific effectsBroad-spectrum antibioticsAnaerobic gut microbiotaTh17 cellsIL-17Infectious triggerPathogenic autoantibodiesPulmonary emboliIL-10IL-21Myocardial infarctionIL-1BSplenocyte proliferationAntibody productionMicrobiota compositionImmune systemAutoimmunityMicrobiotaAutoimmune 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