Featured Publications
m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity
Qin Y, Li B, Arumugam S, Lu Q, Mankash SM, Li J, Sun B, Li J, Flavell RA, Li HB, Ouyang X. m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity. Cell Reports 2021, 37: 109968. PMID: 34758326, PMCID: PMC8667589, DOI: 10.1016/j.celrep.2021.109968.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseProgression of NAFLDLineage-restricted deletionFatty liver diseaseMultiple mRNA transcriptsMyeloid cell activationDiet-induced developmentMethyladenosine (m<sup>6</sup>A) RNA modificationMRNA metabolismProtein methyltransferaseLiver diseaseRNA modificationsCellular stressMetabolic reprogrammingDDIT4 mRNACell activationObesityDifferential expressionMammalian targetMRNA transcriptsSignificant downregulationCytokine stimulationPathway activityMetabolic phenotypeMRNA levelsDigoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation
Zhao P, Han SN, Arumugam S, Yousaf MN, Qin Y, Jiang JX, Torok NJ, Chen Y, Mankash MS, Liu J, Li J, Iwakiri Y, Ouyang X. Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation. AJP Gastrointestinal And Liver Physiology 2019, 317: g387-g397. PMID: 31411894, PMCID: PMC6842989, DOI: 10.1152/ajpgi.00054.2019.Peer-Reviewed Original ResearchConceptsHigh-fat dietSignificant clinical applicabilityHuman nonalcoholic steatohepatitisNonalcoholic steatohepatitisOral digoxinLiver injuryCell subsetsPathway activationMouse modelHigh-fat diet mouse modelLiver injury mouse modelHepatocyte mitochondrial dysfunctionClinical applicabilityDiet mouse modelInjury mouse modelDifferential involvementLarge clinical experienceNLRP3 inflammasome activationSignificant protective effectHIF-1α transactivationHepatic oxidative stress responseHypoxia-inducible factorLiver inflammationHFD miceWide dosage rangeDigoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis
Ouyang X, Han SN, Zhang JY, Dioletis E, Nemeth BT, Pacher P, Feng D, Bataller R, Cabezas J, Stärkel P, Caballeria J, Pongratz RL, Cai SY, Schnabl B, Hoque R, Chen Y, Yang WH, Garcia-Martinez I, Wang FS, Gao B, Torok NJ, Kibbey RG, Mehal WZ. Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis. Cell Metabolism 2018, 27: 339-350.e3. PMID: 29414684, PMCID: PMC5806149, DOI: 10.1016/j.cmet.2018.01.007.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell NucleusChromatinDigoxinDisease Models, AnimalEndotoxinsHistonesHumansHypoxia-Inducible Factor 1, alpha SubunitInflammationLiverNon-alcoholic Fatty Liver DiseaseOxidation-ReductionProtein BindingPyruvate KinaseTHP-1 CellsTranscription, GeneticTranscriptional ActivationConceptsHIF-1α transactivationSterile inflammationHIF-1α pathway activationNon-alcoholic steatohepatitisKinase M2Major clinical consequencesAbility of digoxinLiver inflammationLiver diseasePyruvate kinase M2Clinical consequencesTherapeutic targetInflammationTissue damageHIF-1αPathway activationDigoxinOxidative stressCardiac glycosidesSteatohepatitisDigoxin bindsNovel roleLiverUbiquitous responseActivationThe DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury
Hu B, Jin C, Li HB, Tong J, Ouyang X, Cetinbas NM, Zhu S, Strowig T, Lam FC, Zhao C, Henao-Mejia J, Yilmaz O, Fitzgerald KA, Eisenbarth SC, Elinav E, Flavell RA. The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. Science 2016, 354: 765-768. PMID: 27846608, PMCID: PMC5640175, DOI: 10.1126/science.aaf7532.Peer-Reviewed Original ResearchConceptsCell deathDNA sensor AIM2New therapeutic targetsCaspase-1-dependent deathIntestinal epithelial cellsBone marrow cellsGastrointestinal syndromeTissue injuryInflammasome activationGastrointestinal tractRadiation-induced cell deathRadiation-induced DNA damageTherapeutic targetAcute exposureBone marrowChemotherapeutic agentsMarrow cellsRadiation exposureAIM2Massive cell deathEpithelial cellsHematopoietic failureDeathMolecular mechanismsDNA damageAdenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway
Ouyang X, Ghani A, Malik A, Wilder T, Colegio OR, Flavell RA, Cronstein BN, Mehal WZ. Adenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway. Nature Communications 2013, 4: 2909. PMID: 24352507, PMCID: PMC3895487, DOI: 10.1038/ncomms3909.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAdenosine TriphosphateAnimalsCarrier ProteinsCyclic AMPCyclic AMP Response Element-Binding ProteinCyclic AMP-Dependent Protein KinasesHypoxia-Inducible Factor 1, alpha SubunitInflammasomesInterleukin-1betaLipopolysaccharidesLiverMacrophagesMaleMiceMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinReceptor, Adenosine A2ASignal TransductionConceptsHIF-1α pathwayInflammasome activityInflammasome activationA2A receptorsIL-1β productionIL-1β responseReceptor-mediated signalingLack of responseTolerogenic stateChronic diseasesInflammatory responseInflammasome pathwayPrevious exposureLipopolysaccharideAdenosineReceptorsActivationKey regulatorInitial activationPathwaySignalingResponseInterleukinStimuliDisease
2022
RNA m6A demethylase ALKBH5 regulates the development of γδ T cells
Ding C, Xu H, Yu Z, Roulis M, Qu R, Zhou J, Oh J, Crawford J, Gao Y, Jackson R, Sefik E, Li S, Wei Z, Skadow M, Yin Z, Ouyang X, Wang L, Zou Q, Su B, Hu W, Flavell RA, Li HB. RNA m6A demethylase ALKBH5 regulates the development of γδ T cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2203318119. PMID: 35939687, PMCID: PMC9388086, DOI: 10.1073/pnas.2203318119.Peer-Reviewed Original ResearchConceptsDemethylase ALKBH5Messenger RNAΓδ T cellsΓδ T cell biologyCommon posttranscriptional modificationΓδ T cell developmentT cell biologyT cell developmentCell precursorsT cell precursorsMammalian cellsRNA modificationsPosttranscriptional modificationsTissue homeostasisCell biologyT cellsTarget genesCheckpoint roleCell developmentM6A demethylase ALKBH5ALKBH5Γδ T-cell originΓδ T cell repertoireCell populationsEarly developmentSEMA7AR148W mutation promotes lipid accumulation and NAFLD progression via increased localization on the hepatocyte surface
Zhao N, Zhang X, Ding J, Pan Q, Zheng MH, Liu WY, Luo G, Qu J, Li M, Li L, Cheng Y, Peng Y, Xie Q, Wei Q, Li Q, Zou L, Ouyang X, Cai SY, Boyer JL, Chai J. SEMA7AR148W mutation promotes lipid accumulation and NAFLD progression via increased localization on the hepatocyte surface. JCI Insight 2022, 7: e154113. PMID: 35938531, PMCID: PMC9462498, DOI: 10.1172/jci.insight.154113.Peer-Reviewed Original ResearchConceptsIntegrin β1Lipid accumulationPrimary mouse hepatocytesProtein interactionsLipid droplet accumulationMouse liverFatty acid oxidationHeterozygous mutationsIntegrin β1 proteinPKC-α phosphorylationFA uptakeGenetic determinantsMouse peritoneal macrophagesCell membraneStrong genetic determinantsMutationsMouse hepatocytesDroplet accumulationΒ1 proteinCD36 expressionAcid oxidationPKCTriglyceride synthesisGenetic polymorphismsAccumulationRevisiting the Principles of Preservation in an Era of Pandemic Obesity
Langford JT, DiRito JR, Doilicho N, Chickering GR, Stern DA, Ouyang X, Mehal W, Tietjen GT. Revisiting the Principles of Preservation in an Era of Pandemic Obesity. Frontiers In Immunology 2022, 13: 830992. PMID: 35432296, PMCID: PMC9011385, DOI: 10.3389/fimmu.2022.830992.Peer-Reviewed Original ResearchConceptsDeceased donorsOrgan preservationDonor populationIschemia-reperfusion injuryCurrent obesity epidemicHealthy donor populationPandemic obesityObese donorsReperfusion injuryMetabolic dysfunctionObesity epidemicObesitySignificant declineOrgansDonorsPopulationCurrent practiceDysfunctionTransplantInjury
2020
Glycogen synthase kinase-3β inhibition alleviates activation of the NLRP3 inflammasome in myocardial infarction
Wang S, Su X, Xu L, Chang C, Yao Y, Komal S, Cha X, Zang M, Ouyang X, Zhang L, Han S. Glycogen synthase kinase-3β inhibition alleviates activation of the NLRP3 inflammasome in myocardial infarction. Journal Of Molecular And Cellular Cardiology 2020, 149: 82-94. PMID: 32991876, DOI: 10.1016/j.yjmcc.2020.09.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCARD Signaling Adaptor ProteinsEnzyme ActivationFibroblastsGlycogen Synthase Kinase 3 betaIndolesInflammasomesInflammationMaleMaleimidesMyocardial InfarctionMyocardial IschemiaMyocytes, CardiacNLR Family, Pyrin Domain-Containing 3 ProteinProtein Kinase InhibitorsProtein MultimerizationRats, Sprague-DawleyVascular RemodelingConceptsNLRP3 inflammasome activationGSK-3β inhibitionMyocardial infarctionInflammasome activationNOD-like receptor family pyrin domainGSK-3βFamily pyrin domainGlycogen synthase kinase-3β inhibitionCardiac dysfunctionMyocardial dysfunctionCardiac damageHeart dysfunctionHeart diseaseSterile inflammationInflammatory responseRat modelDay 2Pyrin domainCardiac fibroblastsSuccessful inductionHypoxia treatmentDysfunctionGSK-3 activityHuman cardiomyocytesInflammasome stimulation
2019
Inflammasome Is Activated in the Liver of Cholestatic Patients and Aggravates Hepatic Injury in Bile Duct–Ligated Mouse
Cai SY, Ge M, Mennone A, Hoque R, Ouyang X, Boyer JL. Inflammasome Is Activated in the Liver of Cholestatic Patients and Aggravates Hepatic Injury in Bile Duct–Ligated Mouse. Cellular And Molecular Gastroenterology And Hepatology 2019, 9: 679-688. PMID: 31887435, PMCID: PMC7160576, DOI: 10.1016/j.jcmgh.2019.12.008.Peer-Reviewed Original ResearchConceptsWT BDL miceCholestatic liver injuryBDL liversBDL miceBile duct ligationBile acidsLiver injuryCholestatic patientsIL-1βM2 anti-inflammatory macrophagesPrimary sclerosing cholangitisPlasma IL-1βLiver hydroxyproline contentLiver of patientsPrimary biliary cholangitisHealthy control subjectsCD206-positive cellsAnti-inflammatory macrophagesIL-1β inductionEndogenous bile acidsCaspase-1 cleavageProcaspase-1 cleavageMouse hepatocytesSclerosing cholangitisLiver histology
2018
β-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway
Chen Y, Ouyang X, Hoque R, Garcia-Martinez I, Yousaf MN, Tonack S, Offermanns S, Dubuquoy L, Louvet A, Mathurin P, Massey V, Schnabl B, Bataller R, Mehal WZ. β-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway. Journal Of Hepatology 2018, 69: 687-696. PMID: 29705237, PMCID: PMC6098974, DOI: 10.1016/j.jhep.2018.04.004.Peer-Reviewed Original ResearchConceptsAlcohol-induced liver injuryAlcoholic hepatitisAlanine aminotransferase levelsLiver injuryNeutrophil influxAminotransferase levelsΒ-hydroxybutyrateDevelopment of AHPlasma alanine aminotransferase levelsGreater neutrophil influxExcess alcohol intakeAlcoholic liver diseaseLife-threatening conditionExcess alcohol consumptionDependent pathwayHigher plasma alanine aminotransferase levelsIntrahepatic macrophagesLiver inflammationLiver diseaseAlcohol intakeHepatoprotective roleReduced steatosisM2 phenotypeTherapeutic effectHepatitis
2017
An endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of kupffer cell polarization
Park J, Shao M, Kim MY, Baik SK, Cho MY, Utsumi T, Satoh A, Ouyang X, Chung C, Iwakiri Y. An endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of kupffer cell polarization. Hepatology 2017, 65: 1720-1734. PMID: 28090670, PMCID: PMC5397326, DOI: 10.1002/hep.29051.Peer-Reviewed Original ResearchConceptsAlcoholic liver diseasePositive Kupffer cellsKupffer cellsLiver injuryALD patientsLiver diseaseM1 polarizationKO miceM2 polarizationLieber-DeCarli ethanol liquid dietDisease severityM1/M2 polarizationKupffer cell polarizationEthanol liquid dietHepatic triglyceride levelsM2 macrophage polarizationHigher hepatic triglyceride levelsChronic ethanol feedingNew therapeutic targetsER stressAbsence of NogoM2 statusWT miceM1 activationTriglyceride levelsBile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response
Cai SY, Ouyang X, Chen Y, Soroka CJ, Wang J, Mennone A, Wang Y, Mehal WZ, Jain D, Boyer JL. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight 2017, 2: e90780. PMID: 28289714, PMCID: PMC5333973, DOI: 10.1172/jci.insight.90780.Peer-Reviewed Original ResearchConceptsLiver injuryInflammatory responseBile acid-induced liver injuryCholestatic liver injuryInflammatory liver injuryProinflammatory cytokine expressionCholestatic liver diseaseBile duct ligationVivo mouse modelHepatic infiltrationInflammatory injurySerum aminotransferasesLiver diseaseCholestatic patientsCytokine expressionChemokine inductionPathophysiologic concentrationsNeutrophil chemotaxisDuct ligationPathophysiologic levelsMouse modelNew therapiesInnate immunityInjuryPeriportal areas
2016
The SGLT‐2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− Mice
Leng W, Ouyang X, Lei X, Wu M, Chen L, Wu Q, Deng W, Liang Z. The SGLT‐2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− Mice. Mediators Of Inflammation 2016, 2016: 6305735. PMID: 28104929, PMCID: PMC5220517, DOI: 10.1155/2016/6305735.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaApolipoproteins EAtherosclerosisBenzhydryl CompoundsBlood GlucoseBone MarrowDiabetes ComplicationsDiabetes Mellitus, ExperimentalGlucoseGlucosidesInflammasomesInterleukin-18Interleukin-1betaMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinReactive Oxygen SpeciesSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsConceptsEffect of dapagliflozinHigh-fat dietIL-1Dapagliflozin treatmentDiabetic atherosclerosisInhibitor dapagliflozinIL-18Reactive oxygen speciesSodium-glucose cotransporter 2 inhibitor dapagliflozinFat metabolismSGLT-2 inhibitor dapagliflozinCaspase-1 pathwayIndices of glucoseHematoxylin-eosin stainingStability of lesionsFormation of atherosclerosisNLRP3 protein levelsOil Red ODiabetic ApoEROS-NLRP3Aortic atherosclerosisMacrophage infiltrationNLRP3 inflammasomeTherapeutic effectMitochondrial reactive oxygen species
2015
Na+/H+ exchanger regulatory factor 1 knockout mice have an attenuated hepatic inflammatory response and are protected from cholestatic liver injury
Li M, Mennone A, Soroka CJ, Hagey LR, Ouyang X, Weinman EJ, Boyer JL. Na+/H+ exchanger regulatory factor 1 knockout mice have an attenuated hepatic inflammatory response and are protected from cholestatic liver injury. Hepatology 2015, 62: 1227-1236. PMID: 26108984, PMCID: PMC4589453, DOI: 10.1002/hep.27956.Peer-Reviewed Original ResearchConceptsBile duct ligationLiver injuryInflammatory responseICAM-1BDL miceBDL-induced liver injuryNeutrophil-mediated liver injuryTotal bile acid concentrationTumor necrosis factor alphaIntercellular adhesion molecule-1Hepatic neutrophil accumulationAttenuated liver injuryCholestatic liver injuryHepatic inflammatory responseMouse liverSerum alanine aminotransferaseBile acid concentrationsHepatic inflammatory diseasesICAM-1 expressionNecrosis factor alphaAdhesion molecule-1Wild-type miceICAM-1 proteinNew therapeutic targetsMessenger RNA levels
2014
Effect of osteopontin in regulating bone marrow mesenchymal stem cell treatment of skin wounds in diabetic mice
Meng H, Wang Z, Wang W, Li W, Wu Q, Lei X, Ouyang X, Liang Z. Effect of osteopontin in regulating bone marrow mesenchymal stem cell treatment of skin wounds in diabetic mice. Diabetes/Metabolism Research And Reviews 2014, 30: 457-466. PMID: 24827928, DOI: 10.1002/dmrr.2566.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementCells, CulturedDiabetes Mellitus, ExperimentalFetal Stem CellsGreen Fluorescent ProteinsMaleMesenchymal Stem Cell TransplantationMesenchymal Stem CellsMice, Inbred C57BLMice, KnockoutMice, TransgenicMicrovesselsNeovascularization, PhysiologicOsteopontinRandom AllocationRecombinant Fusion ProteinsSkinWound HealingWounds, PenetratingConceptsWT mesenchymal stem cellsMesenchymal stem cellsHealing timeNormal miceDiabetic miceSkin woundsBone marrow mesenchymal stem cell treatmentMesenchymal stem cell treatmentStem cellsWestern blottingHealing woundsKO male miceWild-type miceWounds of miceDiabetic skin woundsRole of osteopontinStem cell treatmentEffect of osteopontinExpression of osteopontinBacks of miceDiabetes mellitusIntraperitoneal injectionMale miceMicrovessel densityTail veinActivation of N-methyl-d-aspartate receptor downregulates inflammasome activity and liver inflammation via a β-arrestin-2 pathway
Farooq A, Hoque R, Ouyang X, Farooq A, Ghani A, Ahsan K, Guerra M, Mehal WZ. Activation of N-methyl-d-aspartate receptor downregulates inflammasome activity and liver inflammation via a β-arrestin-2 pathway. AJP Gastrointestinal And Liver Physiology 2014, 307: g732-g740. PMID: 25104498, PMCID: PMC4187065, DOI: 10.1152/ajpgi.00073.2014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsArrestinsAspartic AcidBeta-Arrestin 2Beta-ArrestinsCarrier ProteinsCaspase 1Cell LineChemical and Drug Induced Liver InjuryDisease Models, AnimalExcitatory Amino Acid AgonistsHumansInflammasomesInterleukin-1betaLiverMacrophagesMaleMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinPancreatitisProtein PrecursorsReceptors, N-Methyl-D-AspartateSignal TransductionTime FactorsConceptsNMDA receptorsAcute hepatitisLiver inflammationInflammasome activityAcute inflammatory liver injuryNOD-like receptor familyN-methyl-D-aspartate (NMDA) receptor familyChronic liver inflammationInflammatory liver injuryΒ-arrestinBrain NMDA receptorsReceptor familyNMDA receptor pathwayLigand-gated ion channelsLiver injuryNonalcoholic steatohepatitisImmune suppressionLimits injuryNF-kβImmune regulationInflammasome activationKupffer cellsInflammasome machineryPyrin domainNonneuronal cellsImmune Chaperone gp96 Drives the Contributions of Macrophages to Inflammatory Colon Tumorigenesis
Morales C, Rachidi S, Hong F, Sun S, Ouyang X, Wallace C, Zhang Y, Garret-Mayer E, Wu J, Liu B, Li Z. Immune Chaperone gp96 Drives the Contributions of Macrophages to Inflammatory Colon Tumorigenesis. Cancer Research 2014, 74: 446-459. PMID: 24322981, PMCID: PMC4002507, DOI: 10.1158/0008-5472.can-13-1677.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow CellsCell Transformation, NeoplasticColitisColonColonic NeoplasmsCrosses, GeneticCytokinesDisease ProgressionDNA RepairGene DeletionGene Expression Regulation, NeoplasticInflammationInterleukin-17Interleukin-23MacrophagesMaleMembrane GlycoproteinsMiceMice, KnockoutMucous MembraneConceptsDNA repair machineryDNA repair pathwaysColon tumorigenesisTumor-associated macrophagesRepair machineryRepair pathwaysOncogenic programEndoplasmic reticulumMutation rateChaperone gp96Β-cateninColon cancerMechanistic underpinningsCellular sitesTumorigenesisReduced expressionEpithelial cellsGenotoxic natureToll-like receptorsInflammation-associated colon cancerImportant driverGp96Inflammation-associated colon tumorigenesisCritical inflammatory cytokinesExpression
2011
Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body response
Malik AF, Hoque R, Ouyang X, Ghani A, Hong E, Khan K, Moore LB, Ng G, Munro F, Flavell RA, Shi Y, Kyriakides TR, Mehal WZ. Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body response. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 20095-20100. PMID: 22109549, PMCID: PMC3250158, DOI: 10.1073/pnas.1105152108.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnimalsApoptosis Regulatory ProteinsAspirinBiocompatible MaterialsCalcium-Binding ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cluster AnalysisCytoskeletal ProteinsForeign-Body ReactionGiant CellsInflammasomesInflammationInterleukin-1betaMacrophages, PeritonealMembrane MicrodomainsMiceMice, Inbred C57BLMicrospheresNLR Family, Pyrin Domain-Containing 3 ProteinPolymethyl MethacrylateTranscription factor IRF8 directs a silencing programme for TH17 cell differentiation
Ouyang X, Zhang R, Yang J, Li Q, Qin L, Zhu C, Liu J, Ning H, Shin MS, Gupta M, Qi CF, He JC, Lira SA, Morse HC, Ozato K, Mayer L, Xiong H. Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation. Nature Communications 2011, 2: 314. PMID: 21587231, PMCID: PMC3112536, DOI: 10.1038/ncomms1311.Peer-Reviewed Original ResearchConceptsTh17 cell differentiationRegulatory factor familyTranscription factor IRF8T cell-specific deletionCritical roleFunctional diversityLineage commitmentTranscription factorsCell-specific deletionFactor familyTranscriptional inhibitorIRF8 geneMolecular mechanismsCell differentiationConventional knockoutIRF8IRF8 deficiencyPhysical interactionDifferentiationTh17 cellsPathogenesis of autoimmunityCellsGenesUnique subsetDiversity