2020
Immune Cells in the Placental Villi Contribute to Intra-amniotic Inflammation
Toothaker JM, Presicce P, Cappelletti M, Stras SF, McCourt CC, Chougnet CA, Kallapur SG, Konnikova L. Immune Cells in the Placental Villi Contribute to Intra-amniotic Inflammation. Frontiers In Immunology 2020, 11: 866. PMID: 32528468, PMCID: PMC7256198, DOI: 10.3389/fimmu.2020.00866.Peer-Reviewed Original ResearchConceptsFetal-maternal interfaceIntra-amniotic inflammationImmune cellsVillous placentaT cellsPlacental villiNatural killerTumor necrosis factor alphaAbundance of neutrophilsIA LPS exposureCD8 T cellsMemory T cellsAntigen-presenting cellsRhesus macaque modelNecrosis factor alphaDistinct immunological profilePotential therapeutic targetTNFα blockadeLPS exposureSignificant morbidityMacaque modelProinflammatory cytokinesImmunological profileFactor alphaImmunological responseSingle-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn’s Disease
Mitsialis V, Wall S, Liu P, Ordovas-Montanes J, Parmet T, Vukovic M, Spencer D, Field M, McCourt C, Toothaker J, Bousvaros A, Center B, Ballal S, Bonilla S, Fawaz R, Fishman L, Flores A, Fox V, Grover A, Higuchi L, Huh S, Kahn S, Lee C, Mobassaleh M, Ouahed J, Pleskow R, Regan B, Rufo P, Sabharwal S, Silverstein J, Verhave M, Wolf A, Zimmerman L, Zitomersky N, Center B, Allegretti J, De Silva P, Friedman S, Hamilton M, Korzenik J, Makrauer F, Norton B, Winter R, Shalek A, Kean L, Horwitz B, Goldsmith J, Tseng G, Snapper S, Konnikova L. Single-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn’s Disease. Gastroenterology 2020, 159: 591-608.e10. PMID: 32428507, PMCID: PMC8166295, DOI: 10.1053/j.gastro.2020.04.074.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseasePeripheral blood mononuclear cellsActive Crohn's diseaseBlood mononuclear cellsColonic mucosa samplesActive ulcerative colitisPlasmacytoid dendritic cellsInnate lymphoid cellsUlcerative colitisCrohn's diseaseDendritic cellsImmune cell populationsRegulatory cellsMononuclear cellsT cellsMucosa samplesBlood samplesLymphoid cellsGroup 1 innate lymphoid cellsType 3 innate lymphoid cellsEffector memory T cellsCell populationsInactive ulcerative colitisInactive Crohn's diseaseMemory T cells
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 cytometryA Unique Presentation of Infantile-Onset Colitis and Eosinophilic Disease without Recurrent Infections Resulting from a Novel Homozygous CARMIL2 Variant
Kurolap A, Eshach Adiv O, Konnikova L, Werner L, Gonzaga-Jauregui C, Steinberg M, Mitsialis V, Mory A, Nunberg MY, Wall S, Shaoul R, Overton JD, Shuldiner A, Zohar Y, Paperna T, Snapper S, Shouval D, Baris Feldman H. A Unique Presentation of Infantile-Onset Colitis and Eosinophilic Disease without Recurrent Infections Resulting from a Novel Homozygous CARMIL2 Variant. Journal Of Clinical Immunology 2019, 39: 430-439. PMID: 31079270, DOI: 10.1007/s10875-019-00631-6.Peer-Reviewed Original ResearchMeSH KeywordsAge of OnsetAmino Acid SequenceChildChild, PreschoolColitisDNA Mutational AnalysisEnteritisEosinophiliaExome SequencingGastritisGenetic Association StudiesGenetic Predisposition to DiseaseHomozygoteHumansImmunohistochemistryImmunophenotypingMaleMicrofilament ProteinsModels, MolecularMutationPhenotypeStructure-Activity RelationshipConceptsWhole-exome sequencingImmunological workupWestern blotRecurrent infectionsGastrointestinal diseasesCyTOF analysisRegulatory T cell frequencyEosinophilic gastrointestinal diseasesEosinophilic gastrointestinal disordersT cell frequenciesUlcerative colitis patientsAdaptive immune cellsEvidence of recurrentSigns of immunodeficiencyT cell proliferationT-cell studiesColitis patientsChronic diarrheaImmunodeficiency syndromeTreg generationGastrointestinal disordersImmunological phenotypeImmune populationsImmune cellsSevere infections
2018
High-dimensional immune phenotyping and transcriptional analyses reveal robust recovery of viable human immune and epithelial cells from frozen gastrointestinal tissue
Konnikova L, Boschetti G, Rahman A, Mitsialis V, Lord J, Richmond C, Tomov VT, Gordon W, Jelinsky S, Canavan J, Liss A, Wall S, Field M, Zhou F, Goldsmith JD, Bewtra M, Breault DT, Merad M, Snapper SB. High-dimensional immune phenotyping and transcriptional analyses reveal robust recovery of viable human immune and epithelial cells from frozen gastrointestinal tissue. Mucosal Immunology 2018, 11: 1684-1693. PMID: 30111863, PMCID: PMC6512331, DOI: 10.1038/s41385-018-0047-y.Peer-Reviewed Original ResearchMeSH KeywordsCell SurvivalCryopreservationGene Expression ProfilingHumansImmunophenotypingIntestinal MucosaIntestinesConceptsImmune cellsGastrointestinal tissuesMucosal immune compartmentPeripheral immune cellsMucosal immune cellsEpithelial cellsImmune compartmentImmune phenotypingTreatment responsivenessMucosal tissuesTranslational studiesDisease pathogenesisSimple storage techniquesPreservation of viabilityPathogenesisTissueBiomarker discoveryCellsDisease