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
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
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