2024
Single-cell atlas of the small intestine throughout the human lifespan demonstrates unique features of fetal immune cells
Gu W, Eke C, Santiago E, Olaloye O, Konnikova L. Single-cell atlas of the small intestine throughout the human lifespan demonstrates unique features of fetal immune cells. Mucosal Immunology 2024, 17: 599-617. PMID: 38555026, PMCID: PMC11384551, DOI: 10.1016/j.mucimm.2024.03.011.Peer-Reviewed Original ResearchImmune cellsDevelopment of mucosal immunityComplex immune landscapeFetal immune cellsSevere intestinal complicationsComplications of prematurityMemory T cellsAdaptive immune cellsMucosal immune cellsSmall intestineT cell statesMemory T cell statesStem-like propertiesNecrotizing enterocolitisNeonatal samplesMyeloid populationsImmune landscapeFetal samplesT cellsExpression of activationPostnatal samplesMucosal diseaseMucosal immunitySingle-cell RNA sequencingSingle-cell atlas
2022
RIPK1 mutations causing infantile-onset IBD with inflammatory and fistulizing features
Sultan M, Adawi M, Kol N, McCourt B, Adawi I, Baram L, Tal N, Werner L, Lev A, Snapper S, Barel O, Konnikova L, Somech R, Shouval D. RIPK1 mutations causing infantile-onset IBD with inflammatory and fistulizing features. Frontiers In Immunology 2022, 13: 1041315. PMID: 36466854, PMCID: PMC9716469, DOI: 10.3389/fimmu.2022.1041315.Peer-Reviewed Original ResearchConceptsInfantile-onset inflammatory bowel diseaseReceptor-interacting serine/threonine-protein kinase 1Serine/threonine-protein kinase 1Peripheral blood mononuclear cellsRole of RIPK1Immune cellsMultiple cell typesRIPK1 deficiencyKinase domainCrohn's diseasePatient 1Patient 2Perianal fistulasT cellsGenetic analysisProtein modelingKinase 1B cellsGenetic studiesAllogeneic hematopoietic stem cell transplantationPatients' peripheral blood mononuclear cellsImportant regulatorHematopoietic stem cell transplantationPathogenic genetic variantsCell typesImmune landscape of human placental villi using single-cell analysis
Toothaker JM, Olaloye O, McCourt BT, McCourt CC, Silva TN, Case RM, Liu P, Yimlamai D, Tseng G, Konnikova L. Immune landscape of human placental villi using single-cell analysis. Development 2022, 149 PMID: 35050308, PMCID: PMC8935213, DOI: 10.1242/dev.200013.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, MyelomonocyticB7-H1 AntigenB-LymphocytesChorionic VilliFemaleFetusFlow CytometryHLA-DR AntigensHumansKiller Cells, NaturalLeukocyte Common AntigensLymphocyte ActivationMacrophagesMemory T CellsPlacentaPregnancyPregnancy Trimester, SecondReceptors, Cell SurfaceReceptors, ChemokineSingle-Cell AnalysisT-LymphocytesConceptsT cellsHuman placental villiPlacental villiImmune systemFetal immune systemMaternal immune systemFetal immune cellsAdult T-cellT cell receptor stimulationCell receptor stimulationHealthy pregnancyImmune landscapeMemory phenotypeImmune cellsFetal organsEnhanced proliferative capacityReceptor stimulationMultiple subtypesPV tissueComplex immune systemImaging modalitiesMass cytometryProliferative capacityMaternal mechanismsRecent reportsDOP64 Pathogenic RIPK1 Mutations Cause Infantile-onset IBD with Inflammatory and Fistulizing Features
Sultan M, Millman P, McCourt B, Kol N, Lev A, Matar M, Barel O, Shamir R, Wilschanski M, Konnikova L, Somech R, Shouval D. DOP64 Pathogenic RIPK1 Mutations Cause Infantile-onset IBD with Inflammatory and Fistulizing Features. Journal Of Crohn's And Colitis 2022, 16: i109-i109. DOI: 10.1093/ecco-jcc/jjab232.103.Peer-Reviewed Original ResearchInfantile-onset inflammatory bowel diseaseInflammatory bowel diseasePeripheral blood mononuclear cellsImmune cellsMass cytometry timePerianal fistulasCytometry timeSevere infantile-onset inflammatory bowel diseaseB cellsAllogeneic hematopoietic stem cell transplantationPatients' peripheral blood mononuclear cellsSevere inflammatory bowel diseaseHematopoietic stem cell transplantationIL-1 receptor antagonistMultiple perianal fistulasHyper-inflammatory responseIntestinal immune responsePatient's immune cellsStem cell transplantationBlood mononuclear cellsPeripheral immune dysregulationIL-6 productionRole of RIPK1Cytokine secretion analysisSanger sequencing
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 response
2019
A 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 infectionsHigh-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
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 ResearchConceptsImmune cellsGastrointestinal tissuesMucosal immune compartmentPeripheral immune cellsMucosal immune cellsEpithelial cellsImmune compartmentImmune phenotypingTreatment responsivenessMucosal tissuesTranslational studiesDisease pathogenesisSimple storage techniquesPreservation of viabilityPathogenesisTissueBiomarker discoveryCellsDisease
2016
Interleukin 1β Mediates Intestinal Inflammation in Mice and Patients With Interleukin 10 Receptor Deficiency
Shouval DS, Biswas A, Kang YH, Griffith AE, Konnikova L, Mascanfroni ID, Redhu NS, Frei SM, Field M, Doty AL, Goldsmith JD, Bhan AK, Loizides A, Weiss B, Yerushalmi B, Yanagi T, Lui X, Quintana FJ, Muise AM, Klein C, Horwitz BH, Glover SC, Bousvaros A, Snapper SB. Interleukin 1β Mediates Intestinal Inflammation in Mice and Patients With Interleukin 10 Receptor Deficiency. Gastroenterology 2016, 151: 1100-1104. PMID: 27693323, PMCID: PMC5124405, DOI: 10.1053/j.gastro.2016.08.055.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAdultAnimalsAntirheumatic AgentsCaspase 8CD4-Positive T-LymphocytesCells, CulturedChild, PreschoolColitisGene Expression RegulationHomeodomain ProteinsHumansImmunity, InnateInflammasomesInflammatory Bowel DiseasesInterferon-gammaInterleukin 1 Receptor Antagonist ProteinInterleukin-10Interleukin-10 Receptor alpha SubunitInterleukin-17Interleukin-1betaLipopolysaccharidesMacrophagesMiceMice, KnockoutMutationNLR Family, Pyrin Domain-Containing 3 ProteinProtein BiosynthesisReceptors, Interleukin-10Signal TransductionTumor Necrosis Factor-alphaConceptsInflammatory bowel diseaseProduction of IL1βBowel diseaseIntestinal inflammationT cellsAllogeneic hematopoietic stem cell transplantationInterleukin-10 Receptor DeficiencyHematopoietic stem cell transplantationStem cell transplantationInnate immune cellsActivation of CD4IL1 receptor antagonistTumor necrosis factorInterleukin-10 receptorProduction of IL1Stimulation of macrophagesImmune productionSpontaneous colitisReceptor deficiencyCell transplantationHistologic responseImmune cellsInterleukin-1βDeficient miceNecrosis factor