2024
Alternative mRNA polyadenylation regulates macrophage hyperactivation via the autophagy pathway
Chen Y, Chen B, Li J, Li H, Wang G, Cai X, Zhang Q, Liu X, Kan C, Wang L, Wang Z, Li H. Alternative mRNA polyadenylation regulates macrophage hyperactivation via the autophagy pathway. Cellular & Molecular Immunology 2024, 21: 1522-1534. PMID: 39537902, PMCID: PMC11607066, DOI: 10.1038/s41423-024-01237-8.Peer-Reviewed Original ResearchThe physiological and pathological roles of RNA modifications in T cells
Deng Y, Zhou J, Li H. The physiological and pathological roles of RNA modifications in T cells. Cell Chemical Biology 2024, 31: 1578-1592. PMID: 38986618, DOI: 10.1016/j.chembiol.2024.06.003.Peer-Reviewed Original ResearchRNA modificationsDynamic chemical modificationsInternal RNA modificationFunctions of mammalian cellsT cell developmentPathological roleRNA transcriptsCellular stimuliMammalian cellsRNA moleculesPost-transcriptionallyT cell biologyT cell survivalT cellsCell developmentCell survivalCell biologyRNAT cell-based immunotherapyCell-based immunotherapyT cell immunityAdaptive immunityCellsDifferentiationCell immunity
2022
RNA methylation in immune cells
Chen Y, Oh M, Flavell R, Li H. RNA methylation in immune cells. Advances In Immunology 2022, 155: 39-94. PMID: 36357012, DOI: 10.1016/bs.ai.2022.08.002.Peer-Reviewed Original ResearchDiverging regulation of Bach2 protein and RNA expression determine cell fate in early B cell response
Hu Q, Xu T, Zhang M, Zhang H, Liu Y, Li H, Chen C, Zheng J, Zhang Z, Li F, Shen N, Zhang W, Melnick A, Huang C. Diverging regulation of Bach2 protein and RNA expression determine cell fate in early B cell response. Cell Reports 2022, 40: 111035. PMID: 35793628, PMCID: PMC9550188, DOI: 10.1016/j.celrep.2022.111035.Peer-Reviewed Original ResearchConceptsBach2 proteinCell fateActivated B cellsMemory B cellsB cellsCell fate choiceDetermines cell fateCell fate outcomesRapamycin complex 1B cell fateEffector cellsGerminal centre B cell fatePivotal transcription factorB cell receptor affinityEarly B cell responsesTranscription factorsDependent translationB cell responsesPrimary humoral responseGC fateMechanistic targetHumoral responseProteinPlasma cellsDifferential dynamicsDENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion
Chen B, Hu J, Hu X, Chen H, Bao R, Zhou Y, Ye Y, Zhan M, Cai W, Li H, Li HB. DENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion. Nature Communications 2022, 13: 2059. PMID: 35440133, PMCID: PMC9018773, DOI: 10.1038/s41467-022-29754-y.Peer-Reviewed Original ResearchConceptsPD-L1 expressionTumor immune evasionImmune evasionReduced PD-L1 expressionDeath ligand 1Tumor-killing activityT cellsTherapeutic targetTumor growthCancer cellsCRISPR/Cas9 screeningLigand 1Cell homeostasisKinase 2ExpressionEvasionCD8ImmunotherapyCellsIFNγDysfunctionRBP dysfunctionTumorsCancerm6A mRNA modification maintains colonic epithelial cell homeostasis via NF-κB–mediated antiapoptotic pathway
Zhang T, Ding C, Chen H, Zhao J, Chen Z, Chen B, Mao K, Hao Y, Roulis M, Xu H, Kluger Y, Zou Q, Ye Y, Zhan M, Flavell RA, Li HB. m6A mRNA modification maintains colonic epithelial cell homeostasis via NF-κB–mediated antiapoptotic pathway. Science Advances 2022, 8: eabl5723. PMID: 35333576, PMCID: PMC8956260, DOI: 10.1126/sciadv.abl5723.Peer-Reviewed Original ResearchConceptsMucosal barrier dysfunctionInflammatory bowel diseaseBarrier dysfunctionColonic epithelial cellsColonic mucosal barrier dysfunctionEpithelial cellsStem cellsNF-κB pathwayPotential therapeutic targetEpithelial cell deathEpithelial cell homeostasisSevere colitisBowel diseaseColonic stem cellsTherapeutic targetMouse colonStem cell apoptosisDysfunctionMajor causeCell apoptosisImportant modulatorPathological processesAntiapoptotic pathwaysSpecific deletionCell homeostasis
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 correlationHomeostasism6A demethylase ALKBH5 controls CD4+ T cell pathogenicity and promotes autoimmunity
Zhou J, Zhang X, Hu J, Qu R, Yu Z, Xu H, Chen H, Yan L, Ding C, Zou Q, Ye Y, Wang Z, Flavell RA, Li HB. m6A demethylase ALKBH5 controls CD4+ T cell pathogenicity and promotes autoimmunity. Science Advances 2021, 7: eabg0470. PMID: 34134995, PMCID: PMC8208713, DOI: 10.1126/sciadv.abg0470.Peer-Reviewed Original ResearchAlkB homolog 5T cell-specific ablationT cellsMRNA stabilityCell-specific ablationMethyladenosine (m<sup>6</sup>A) modificationHomolog 5Pathogenicity of CD4Messenger RNAErasersProtein expressionAdoptive transfer colitisExperimental autoimmune encephalomyelitisHomeostasis of CD4T cell responsesSpecific roleT cell pathogenicityCentral nervous systemPooled CRISPR screening identifies m6A as a positive regulator of macrophage activation
Tong J, Wang X, Liu Y, Ren X, Wang A, Chen Z, Yao J, Mao K, Liu T, Meng FL, Pan W, Zou Q, Liu J, Zhou Y, Xia Q, Flavell RA, Zhu S, Li HB. Pooled CRISPR screening identifies m6A as a positive regulator of macrophage activation. Science Advances 2021, 7: eabd4742. PMID: 33910903, PMCID: PMC8081357, DOI: 10.1126/sciadv.abd4742.Peer-Reviewed Original ResearchConceptsMacrophage activationPotential cancer immunotherapy targetInnate immune cellsFaster tumor growthTNF-α productionInnate immune responseCancer immunotherapy targetCre miceImmune cellsImmunotherapy targetImmune responseLPS stimulationTumor growthBacterial infectionsTop candidate genesDeficient macrophagesMultiple cellular responsesMETTL3 deficiencyActivationUnknown roleMETTL3Negative regulatorBinding proteinCellular responsesRNA binding proteinMultiple Functions of RNA Methylation in T Cells: A Review
Chao Y, Li H, Zhou J. Multiple Functions of RNA Methylation in T Cells: A Review. Frontiers In Immunology 2021, 12: 627455. PMID: 33912158, PMCID: PMC8071866, DOI: 10.3389/fimmu.2021.627455.Peer-Reviewed Original ResearchConceptsRNA methylationRNA modificationsMessenger RNAFate determinationEpigenetic regulationEpigenetic modificationsNoncoding RNAsCell homeostasisUbiquitous mechanismMethylationBiological significanceT cell homeostasisMultiple functionsCell proliferationEssential rolePotential therapeutic strategyRecent findingsRNAImmune responseBiological activityPathological statesT cellsCellsTherapeutic strategiesViral infectionMAP3K2-regulated intestinal stromal cells define a distinct stem cell niche
Wu N, Sun H, Zhao X, Zhang Y, Tan J, Qi Y, Wang Q, Ng M, Liu Z, He L, Niu X, Chen L, Liu Z, Li HB, Zeng YA, Roulis M, Liu D, Cheng J, Zhou B, Ng LG, Zou D, Ye Y, Flavell RA, Ginhoux F, Su B. MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche. Nature 2021, 592: 606-610. PMID: 33658717, DOI: 10.1038/s41586-021-03283-y.Peer-Reviewed Original ResearchConceptsStem cell nicheR-spondin 1Intestinal stromal cellsCell nicheDistinct stem cell nichesIntestinal stem cell nicheStromal cellsIntestinal stem cellsStromal cell populationsTissue homeostasisReactive oxygen speciesIntestinal stemMolecular mechanismsAcute intestinal damageSpecific functionsPrimary cellular sourceStem cellsColon cryptsOxygen speciesCell populationsIntestinal injuryIntestinal damageNicheCellular sourceCellsCross-talk of four types of RNA modification writers defines tumor microenvironment and pharmacogenomic landscape in colorectal cancer
Chen H, Yao J, Bao R, Dong Y, Zhang T, Du Y, Wang G, Ni D, Xun Z, Niu X, Ye Y, Li HB. Cross-talk of four types of RNA modification writers defines tumor microenvironment and pharmacogenomic landscape in colorectal cancer. Molecular Cancer 2021, 20: 29. PMID: 33557837, PMCID: PMC7869236, DOI: 10.1186/s12943-021-01322-w.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorColorectal NeoplasmsCombined Modality TherapyComputational BiologyDisease ManagementDisease SusceptibilityEpithelial-Mesenchymal TransitionGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingPharmacogeneticsPrognosisProportional Hazards ModelsRNA Processing, Post-TranscriptionalTranscription, GeneticTranscriptomeTumor MicroenvironmentConceptsColorectal cancerConsensus molecular subtypesTumor microenvironmentRNA modification patternsTME cell-infiltrating characteristicsWorse patient overall survivalDevelopment of CRCInhibitory immune cellsPD-L1 blockadeEfficacy of immunotherapyCharacteristics of TMEPatients' overall survivalPotential clinical utilityTherapeutic liabilityOverall survivalClinical featuresClinical benefitPatient survivalImmune cellsM2 macrophagesCRC samplesImmune responseMolecular subtypesClinical utilitySurvival advantageThe RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells
Wang Y, He K, Sheng B, Lei X, Tao W, Zhu X, Wei Z, Fu R, Wang A, Bai S, Zhang Z, Hong N, Ye C, Tian Y, Wang J, Li M, Zhang K, Li L, Yang H, Li HB, Flavell RA, Zhu S. The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2017432118. PMID: 33483420, PMCID: PMC7848544, DOI: 10.1073/pnas.2017432118.Peer-Reviewed Original ResearchConceptsRNA helicasesEssential biological processesPaneth cellsRNA helicase DHX15Antimicrobial protein expressionCell-specific functionsViral RNA sensorsRNA splicingHelicasesUlcerative colitis patientsCell-specific depletionDHX15Complete knockoutKey regulatorBiological processesIntestinal epithelial cellsLethality of miceVivo roleEnteric bacteriaRNA sensorsDextran sodiumColitis patientsLack of evidenceAntimicrobial responsesIntestinal inflammation
2020
A special collection of reviews on frontiers in immunology
Xu C, Li HB, Flavell RA. A special collection of reviews on frontiers in immunology. Cell Research 2020, 30: 827-828. PMID: 32859992, PMCID: PMC7454546, DOI: 10.1038/s41422-020-00403-7.Peer-Reviewed Original Researchm6A 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
2019
hnRNPA2B1: a nuclear DNA sensor in antiviral immunity
Zhang X, Flavell RA, Li HB. hnRNPA2B1: a nuclear DNA sensor in antiviral immunity. Cell Research 2019, 29: 879-880. PMID: 31471560, PMCID: PMC6889404, DOI: 10.1038/s41422-019-0226-8.Peer-Reviewed Original ResearchAcylglycerol Kinase Maintains Metabolic State and Immune Responses of CD8+ T Cells
Hu Z, Qu G, Yu X, Jiang H, Teng XL, Ding L, Hu Q, Guo X, Zhou Y, Wang F, Li HB, Chen L, Jiang J, Su B, Liu J, Zou Q. Acylglycerol Kinase Maintains Metabolic State and Immune Responses of CD8+ T Cells. Cell Metabolism 2019, 30: 290-302.e5. PMID: 31204281, DOI: 10.1016/j.cmet.2019.05.016.Peer-Reviewed Original ResearchConceptsAcylglycerol kinasePhosphatidylinositol-3-OH kinasePTEN phosphatase activityRecruitment of PTENCell glycolytic metabolismCell antigen receptorPTEN activityPlasma membranePTEN phosphorylationKinase activityRapamycin (mTOR) signalingMammalian targetPhosphatase activityCell glycolysisCell expansionGlycolytic metabolismCell proliferationMetabolic programmingMetabolic stateAntigen receptorKinaseCritical roleGlycolysisCellsFunctional stateAntiviral immunity: a link to bile acids
Wang J, Flavell RA, Li HB. Antiviral immunity: a link to bile acids. Cell Research 2019, 29: 177-178. PMID: 30778178, PMCID: PMC6460437, DOI: 10.1038/s41422-019-0148-5.Peer-Reviewed Original Research