2020
An Immunologic Mode of Multigenerational Transmission Governs a Gut Treg Setpoint
Ramanan D, Sefik E, Galván-Peña S, Wu M, Yang L, Yang Z, Kostic A, Golovkina T, Kasper D, Mathis D, Benoist C. An Immunologic Mode of Multigenerational Transmission Governs a Gut Treg Setpoint. Cell 2020, 181: 1276-1290.e13. PMID: 32402238, PMCID: PMC7393667, DOI: 10.1016/j.cell.2020.04.030.Peer-Reviewed Original ResearchConceptsDouble-negative feedback loopTreg proportionImmunological modeGut immune responseGut commensalsControlling gut inflammationSpecies levelInbred mouse strainsMulti-generational transmissionTreg-dependent mannerCellular perturbationsRegulatory T cellsDisease susceptibilityNon-epigeneticMaternal transmissionInflammatory disease susceptibilityNon-geneticGut inflammationT cellsGenetic tuningMouse strainsImmune responseMultiple generationsImmune systemFeedback loopEnteric 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
2018
m6A 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
Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice
Tan T, Sefik E, Geva-Zatorsky N, Kua L, Naskar D, Teng F, Pasman L, Ortiz-Lopez A, Jupp R, Wu H, Kasper D, Benoist C, Mathis D. Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e8141-e8150. PMID: 27911839, PMCID: PMC5167147, DOI: 10.1073/pnas.1617460113.Peer-Reviewed Original ResearchConceptsIntestinal Th17 cellsB. adolescentisTh17 cell accumulationTh17 cellsHuman gutBifidobacterium strainsBifidobacterium adolescentisBacterial speciesTranscriptional programsIdentified speciesSymbiont bacteriaCell accumulationProbiotic preparationGut epitheliumInduce Th17 cellsMurine intestineK/BxN mouse modelFunctional microbesInoculation of miceFilamentous bacteriaMicrobesAttending inflammationBacteriaGutAutoimmune arthritis
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
2014
Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut
Morton A, Sefik E, Upadhyay R, Weissleder R, Benoist C, Mathis D. Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 6696-6701. PMID: 24753589, PMCID: PMC4020091, DOI: 10.1073/pnas.1405634111.Peer-Reviewed Original ResearchConceptsIntestinal microbiotaKaede transgenic miceFluorescent reportersIntestinal leukocytesFilamentous bacteriaGutMyeloid populationsK/BxN miceTh17 cellsEndoscopic approachImmune cellsLeukocyte subsetsAutoinflammatory diseasesImmune homeostasisDescending colonTransgenic miceLeukocyte movementLeukocytesMounting evidenceCellsMiceMicrobiotaTraffickingBacteria
2011
Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice
Kriegel MA, Sefik E, Hill JA, Wu HJ, Benoist C, Mathis D. Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 11548-11553. PMID: 21709219, PMCID: PMC3136249, DOI: 10.1073/pnas.1108924108.Peer-Reviewed Original ResearchConceptsDiabetes protectionSFB colonizationSmall intestinal lamina propriaSystemic lymphoid tissuesExperimental autoimmune encephalomyelitisNonobese diabetic (NOD) miceT cell compartmentImmune system alterationsType 1 diabetesDifferent Th subsetsSegmented filamentous bacteriaHost physiological functionsNOD miceAutoimmune encephalomyelitisInflammatory arthritisTh17 cellsTh subsetsAutoimmune responseDiabetic miceLymphoid tissueSI-LPSpontaneous modelT cellsLamina propriaMouse model