2023
IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304319120. PMID: 37459511, PMCID: PMC10372654, DOI: 10.1073/pnas.2304319120.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensCD8-Positive T-LymphocytesHumansImmunologic MemoryLicensureMelanomaMemory T CellsMiceSignal TransductionConceptsIL-7R expressionT cellsIL-7RAntitumor memorySuperior antitumor efficacyCell-based therapiesTumor-specific T cellsAntigen-specific T cellsAntitumor efficacyPowerful antitumor immune responseMarkers of exhaustionTumor-specific CD8Antitumor immune responseIndependent prognostic factorAntitumor immune memoryMemory T cellsMajor risk factorSuperior antitumor activityFunctional CD8Memory CD8Prognostic factorsSurgical resectionAdvanced melanomaLymph nodesNaive mice
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 development
2020
Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity
Jarret A, Jackson R, Duizer C, Healy ME, Zhao J, Rone JM, Bielecki P, Sefik E, Roulis M, Rice T, Sivanathan KN, Zhou T, Solis AG, Honcharova-Biletska H, Vélez K, Hartner S, Low JS, Qu R, de Zoete MR, Palm NW, Ring AM, Weber A, Moor AE, Kluger Y, Nowarski R, Flavell RA. Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity. Cell 2020, 180: 50-63.e12. PMID: 31923399, PMCID: PMC7339937, DOI: 10.1016/j.cell.2019.12.016.Peer-Reviewed Original ResearchConceptsEnteric nervous systemSingle-cell sequencingMucosal barrier immunitySingle-molecule fluorescenceIL-18Non-redundant roleSitu mRNA hybridization studiesEpithelial cellsUnbiased RNA sequencingRNA sequencingProtein responseBarrier immunityNervous systemConfocal microscopyCytokine IL-18Hybridization studiesInvasive bacterial infectionsSalmonella typhimurium infectionSequencingProfound consequencesIntestinal neuronsEnteric neuronsIntestinal immunityMucosal barrierTyphimurium infection
2015
Control of peripheral tolerance by regulatory T cell–intrinsic Notch signaling
Charbonnier L, Wang S, Georgiev P, Sefik E, Chatila T. Control of peripheral tolerance by regulatory T cell–intrinsic Notch signaling. Nature Immunology 2015, 16: 1162-1173. PMID: 26437242, PMCID: PMC4618075, DOI: 10.1038/ni.3288.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsEpigenesis, GeneticFemaleForkhead Transcription FactorsGraft vs Host DiseaseMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, TransgenicMutationPeripheral ToleranceRapamycin-Insensitive Companion of mTOR ProteinReceptor, Notch1Recombinant Fusion ProteinsSignal TransductionTh1 CellsT-Lymphocytes, RegulatoryTranscriptome
2010
Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival
Hand TW, Cui W, Jung YW, Sefik E, Joshi NS, Chandele A, Liu Y, Kaech SM. Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 16601-16606. PMID: 20823247, PMCID: PMC2944719, DOI: 10.1073/pnas.1003457107.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell SurvivalDown-RegulationImmunologic MemoryInterleukin-15Lectins, C-TypeLymphocytic choriomeningitis virusMiceMice, Inbred C57BLMice, Mutant StrainsMice, TransgenicPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, CytokineReceptors, ImmunologicSignal TransductionSTAT5 Transcription FactorConceptsCD8 T cell survivalT cell survivalPI3K/AktIL-15IL-7IL-15 receptor expressionAntiviral CD8 T cellsBCL2 expressionCD8 T cellsMemory precursor cellsProtective memory cellsAkt activationJAK/STAT5Effector cell deathEffector cellsHomeostatic proliferationReceptor expressionT cellsConstitutive Akt activationCell growth pathwaysConstitutive STAT5 activationViral infectionSTAT5 phosphorylationPrecursor cellsSurvival