2021
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 levelsMETTL3-mediated m6A RNA methylation promotes the anti-tumour immunity of natural killer cells
Song H, Song J, Cheng M, Zheng M, Wang T, Tian S, Flavell RA, Zhu S, Li HB, Ding C, Wei H, Sun R, Peng H, Tian Z. METTL3-mediated m6A RNA methylation promotes the anti-tumour immunity of natural killer cells. Nature Communications 2021, 12: 5522. PMID: 34535671, PMCID: PMC8448775, DOI: 10.1038/s41467-021-25803-0.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAnimalsCarcinogenesisCell Line, TumorGene DeletionHomeostasisInterleukin-15Killer Cells, NaturalLymphocytes, Tumor-InfiltratingMethylationMethyltransferasesMice, Inbred C57BLMice, KnockoutNeoplasmsProtein Tyrosine Phosphatase, Non-Receptor Type 11Proto-Oncogene Proteins c-aktRNASignal TransductionTumor MicroenvironmentConceptsAnti-tumor immunityNK cellsTumor-infiltrating NK cellsNK cell infiltrationNatural killer cellsAccelerated tumor developmentExert critical rolesImmunosurveillance functionKiller cellsIL-15Cell infiltrationTumor microenvironmentTumor developmentProtein expressionSuppressed activationM6A RNA methylationEffector moleculesExpression levelsMETTL3Cells altersImmunityM6A methylationCellsPositive correlationHomeostasis
2020
m6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development
Gao Y, Vasic R, Song Y, Teng R, Liu C, Gbyli R, Biancon G, Nelakanti R, Lobben K, Kudo E, Liu W, Ardasheva A, Fu X, Wang X, Joshi P, Lee V, Dura B, Viero G, Iwasaki A, Fan R, Xiao A, Flavell RA, Li HB, Tebaldi T, Halene S. m6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development. Immunity 2020, 52: 1007-1021.e8. PMID: 32497523, PMCID: PMC7408742, DOI: 10.1016/j.immuni.2020.05.003.Peer-Reviewed Original ResearchConceptsDouble-stranded RNADeleterious innate immune responseMammalian hematopoietic developmentEndogenous double-stranded RNAHematopoietic developmentInnate immune responseAbundant RNA modificationMurine fetal liverPattern recognition receptor pathwaysImmune responseProtein codingDsRNA formationRNA modificationsWriter METTL3Hematopoietic defectsPerinatal lethalityNative stateConditional deletionAberrant innate immune responsesLoss of METTL3Hematopoietic failureReceptor pathwayAberrant immune responsePrevents formationFetal livermRNA destabilization by BTG1 and BTG2 maintains T cell quiescence
Hwang SS, Lim J, Yu Z, Kong P, Sefik E, Xu H, Harman CCD, Kim LK, Lee GR, Li HB, Flavell RA. mRNA destabilization by BTG1 and BTG2 maintains T cell quiescence. Science 2020, 367: 1255-1260. PMID: 32165587, DOI: 10.1126/science.aax0194.Peer-Reviewed Original Research
2018
Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome
Yu X, Teng XL, Wang F, Zheng Y, Qu G, Zhou Y, Hu Z, Wu Z, Chang Y, Chen L, Li HB, Su B, Lu L, Liu Z, Sun SC, Zou Q. Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome. Journal Of Experimental Medicine 2018, 215: 2463-2476. PMID: 30115741, PMCID: PMC6122976, DOI: 10.1084/jem.20180397.Peer-Reviewed Original ResearchConceptsCell metabolismPhosphatase catalytic subunitRapamycin complex 1Component raptorRegulatory T Cell StabilityCatalytic subunitMetabolic programsMechanistic targetPivotal regulatorSignaling mechanismTRAF3IP3Metabolic regulatorMetabolic fitnessCell functionRegulatorLysosomesMetabolismT reg cell functionCell stabilityPP2AcComplexes 1RaptorsSubunitsDeletionStrong antitumor T-cell responsesSENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation
Yu X, Lao Y, Teng XL, Li S, Zhou Y, Wang F, Guo X, Deng S, Chang Y, Wu X, Liu Z, Chen L, Lu LM, Cheng J, Li B, Su B, Jiang J, Li HB, Huang C, Yi J, Zou Q. SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation. Nature Communications 2018, 9: 3157. PMID: 30089837, PMCID: PMC6082899, DOI: 10.1038/s41467-018-05676-6.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsAntineoplastic AgentsAutoimmunityBasic-Leucine Zipper Transcription FactorsBone Marrow CellsCD4-Positive T-LymphocytesCell DifferentiationCell Line, TumorCell NucleusCysteine EndopeptidasesFemaleGene DeletionGene Expression ProfilingGene Expression RegulationHEK293 CellsHomeostasisHumansImmune ToleranceLymphocyte ActivationMelanoma, ExperimentalMiceMice, Inbred C57BLMice, KnockoutPeptide HydrolasesReactive Oxygen SpeciesSumoylationT-Lymphocytes, RegulatoryConceptsRegulatory T cellsTreg cellsT cellsReactive oxygen speciesSUMO-specific protease 3T effector cell differentiationAntitumor T-cell responsesTreg cell-specific deletionT cell responsesEffector cell differentiationTreg cell stabilityCell-specific deletionT cell activationImmune toleranceTumor immunosuppressionAutoimmune symptomsImmune homeostasisRegulation of ROSRole of SENP3Cell activationCell responsesGene signatureProtease 3Pivotal regulatorNuclear exportm6A mRNA methylation sustains Treg suppressive functions
Tong J, Cao G, Zhang T, Sefik E, Amezcua Vesely MC, Broughton JP, Zhu S, Li H, Li B, Chen L, Chang HY, Su B, Flavell RA, Li HB. m6A mRNA methylation sustains Treg suppressive functions. Cell Research 2018, 28: 253-256. PMID: 29303144, PMCID: PMC5799823, DOI: 10.1038/cr.2018.7.Peer-Reviewed Original Research
2016
The 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 damage