2020
In utero human intestine harbors unique metabolomic features including bacterial metabolites
Li Y, Toothaker JM, Ben-Simon S, Ozeri L, Schweitzer R, McCourt BT, McCourt CC, Werner L, Snapper SB, Shouval DS, Khatib S, Koren O, Agnihorti S, Tseng G, Konnikova L. In utero human intestine harbors unique metabolomic features including bacterial metabolites. JCI Insight 2020, 5: e138751. PMID: 33001863, PMCID: PMC7710283, DOI: 10.1172/jci.insight.138751.Peer-Reviewed Original ResearchConceptsFetal immune systemIntestinal barrier integrityMicrobial-associated metabolitesHost-derived metabolitesBacterial DNAIntestinal immunityMaternal microbiomeIntestinal functionImmune regulationGastrointestinal tractIntestinal microbiomeFetal intestineBarrier integrityImmune systemHuman intestinal samplesIntestinal samplesIntestinal profileMicrobial encountersMetabolomic featuresBacterial metabolitesUteroNutrient metabolismMetabolitesRecent studiesMicrobiome
2019
Maturation of the Human Intestinal Immune System Occurs Early in Fetal Development
Stras SF, Werner L, Toothaker JM, Olaloye OO, Oldham AL, McCourt CC, Lee YN, Rechavi E, Shouval DS, Konnikova L. Maturation of the Human Intestinal Immune System Occurs Early in Fetal Development. Developmental Cell 2019, 51: 357-373.e5. PMID: 31607651, DOI: 10.1016/j.devcel.2019.09.008.Peer-Reviewed Original ResearchMeSH KeywordsB-LymphocytesCell ProliferationClone CellsCytokinesFemaleFetal DevelopmentFetusHumansImmune SystemImmunity, MucosalImmunologic MemoryImmunophenotypingInfant, NewbornIntestinesPregnancyPregnancy Trimester, SecondReceptors, Antigen, B-CellReceptors, Antigen, T-CellT-LymphocytesV(D)J RecombinationConceptsInnate lymphoid cellsGestational ageIntestinal immunityDendritic cellsB cellsHuman intestinal immune systemAdaptive immune landscapeIntestinal immune systemNatural killer cellsWeeks gestational ageTransitional B cellsB cell maturityT cell receptorComplex innateImmune atlasEarly life developmentImmune landscapeKiller cellsTCR repertoireLymphoid cellsFetal developmentImmune systemInnate immunityCell receptorMass cytometryHigh-dimensional immune atlas of second trimester human intestinal immunity
Konnikova L, Stras S, Werner L, Toothaker J, Oldham A, Shouval D. High-dimensional immune atlas of second trimester human intestinal immunity. The Journal Of Immunology 2019, 202: 67.12-67.12. DOI: 10.4049/jimmunol.202.supp.67.12.Peer-Reviewed Original ResearchT cellsImmune atlasIntestinal immunityB cellsImmune systemTissue-resident memory T cellsLarge intestineResident memory T cellsMucosal immune developmentNeonatal immune systemEffector memory subsetsInnate lymphoid cellsMemory T cellsNatural killer cellsTransitional B cellsT cell receptorFull-term samplesMost newbornsWeeks' gestationAdvanced gestationKiller cellsMucosal immunityNeonatal deathMemory subsetsImmune cells
2018
Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy
Kotlarz D, Marquardt B, Barøy T, Lee WS, Konnikova L, Hollizeck S, Magg T, Lehle AS, Walz C, Borggraefe I, Hauck F, Bufler P, Conca R, Wall SM, Schumacher EM, Misceo D, Frengen E, Bentsen BS, Uhlig HH, Hopfner KP, Muise AM, Snapper SB, Strømme P, Klein C. Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy. Nature Genetics 2018, 50: 344-348. PMID: 29483653, PMCID: PMC6309869, DOI: 10.1038/s41588-018-0063-6.Peer-Reviewed Original ResearchConceptsInfantile inflammatory bowel diseaseInflammatory bowel diseaseTGF-β1Bowel diseaseSevere inflammatory bowel diseaseCentral nervous system diseaseNervous system diseasesRole of TGFPosterior leukoencephalopathyIntestinal immunityBrain atrophySystem diseasesTGFB1 geneBiallelic lossImpaired secretionGrowth factorTGF-β familyDiseaseTGF-β1 deficiencyNonredundant roleFunction mutationsPrototypic memberLeukoencephalopathyAtrophyEpilepsy