2024
The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity
Marin-Lopez A, Huck J, Esterly A, Azcutia V, Rosen C, Garcia-Milian R, Sefik E, Vidal-Pedrola G, Raduwan H, Chen T, Arora G, Halene S, Shaw A, Palm N, Flavell R, Parkos C, Thangamani S, Ring A, Fikrig E. The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity. Science Immunology 2024, 9: eadk9872. PMID: 39121194, DOI: 10.1126/sciimmunol.adk9872.Peer-Reviewed Original ResearchConceptsSuppress antiviral responsesArthropod proteinsPathogen replicationAntiviral responseProtein AVertebrate hostsMosquito salivary proteinsUp-regulatedBlood feedingHuman macrophagesPleomorphic effectsSkin infectionsZika virus disseminationInhibit proinflammatory responsesSalivary proteinsProteinNatural ligandWhite blood cellsHuman skin explantsProinflammatory responseMosquito salivaVirus disseminationHuman CD47Salivary factorsArbovirus infection
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
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
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