2023
Single-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis
Egozi A, Olaloye O, Werner L, Silva T, McCourt B, Pierce R, An X, Wang F, Chen K, Pober J, Shouval D, Itzkovitz S, Konnikova L. Single-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis. PLOS Biology 2023, 21: e3002124. PMID: 37205711, PMCID: PMC10234541, DOI: 10.1371/journal.pbio.3002124.Peer-Reviewed Original ResearchMeSH KeywordsEndothelial CellsEnterocolitis, NecrotizingHumansInfantInfant, NewbornInfant, PrematureIntestinal MucosaIntestine, SmallIntestinesConceptsSingle-cell RNA sequencingSingle-cell atlasEpithelial cellsCell identityRNA sequencingBulk transcriptomicsCellular dysregulationAberrant interactionsNeonatal small intestinePotential targetCellular changesBiomarker discoveryGastrointestinal complicationsPremature infantsProinflammatory macrophagesProinflammatory genesClonal expansionT cellsEndothelial cellsImmune interactionsIntestinal tissueCellsSmall intestineComprehensive viewNECSingle cell analysis via mass cytometry of spontaneous intestinal perforation reveals alterations in small intestinal innate and adaptive mucosal immunity
Olaloye O, Eke C, Jolteus A, Konnikova L. Single cell analysis via mass cytometry of spontaneous intestinal perforation reveals alterations in small intestinal innate and adaptive mucosal immunity. Frontiers In Immunology 2023, 14: 995558. PMID: 36825028, PMCID: PMC9941693, DOI: 10.3389/fimmu.2023.995558.Peer-Reviewed Original ResearchConceptsSpontaneous intestinal perforationMucosal immune dysfunctionSevere gastrointestinal complicationsSmall intestinal mucosaMass cytometry timeGastrointestinal complicationsIntestinal perforationEnteral feedsImmune dysfunctionPremature infantsWeeks' gestationTerminal ileumCytometry timeIntestinal mucosaDisease pathogenesisLocalized perforationFirst weekPatientsSurgeryGestationPerforationPrematurityComplicationsDysfunctionMucosa
2020
Single-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
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 discoveryCellsDiseaseWASP-mediated regulation of anti-inflammatory macrophages is IL-10 dependent and is critical for intestinal homeostasis
Biswas A, Shouval DS, Griffith A, Goettel JA, Field M, Kang YH, Konnikova L, Janssen E, Redhu NS, Thrasher AJ, Chatila T, Kuchroo VK, Geha RS, Notarangelo LD, Pai SY, Horwitz BH, Snapper SB. WASP-mediated regulation of anti-inflammatory macrophages is IL-10 dependent and is critical for intestinal homeostasis. Nature Communications 2018, 9: 1779. PMID: 29725003, PMCID: PMC5934380, DOI: 10.1038/s41467-018-03670-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCell DifferentiationColitisGene DeletionGuanine Nucleotide Exchange FactorsHomeostasisHumansImmunity, MucosalInflammationInterleukin-10Interleukin-1betaInterleukin-23Intestinal MucosaMacrophagesMice, Inbred C57BLMice, TransgenicSignal TransductionWiskott-Aldrich SyndromeWiskott-Aldrich Syndrome ProteinConceptsAnti-inflammatory macrophagesMucosal homeostasisMacrophage functionDevelopment of colitisAbsence of WASpColitis developmentAutoimmune sequelaeDendritic cellsIL-10Immune toleranceIntestinal homeostasisWiskott-Aldrich syndrome proteinMacrophagesMacrophage propertiesSTAT3 phosphorylationColitisExpression of WASPWASP deficiencyHomeostasisDOCK8SequelaeMice
2017
Enhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile-onset IBD
Shouval DS, Konnikova L, Griffith AE, Wall SM, Biswas A, Werner L, Nunberg M, Kammermeier J, Goettel JA, Anand R, Chen H, Weiss B, Li J, Loizides A, Yerushalmi B, Yanagi T, Beier R, Conklin LS, Ebens CL, Santos FGMS, Sherlock M, Goldsmith JD, Kotlarz D, Glover SC, Shah N, Bousvaros A, Uhlig HH, Muise AM, Klein C, Snapper SB. Enhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile-onset IBD. Inflammatory Bowel Diseases 2017, 23: 1950-1961. PMID: 29023267, DOI: 10.1097/mib.0000000000001270.Peer-Reviewed Original ResearchConceptsT cell proliferationDeficient patientsTh17 cellsReceptor deficiencySevere infantile-onset inflammatory bowel diseaseInfantile-onset inflammatory bowel diseaseAdaptive immune cell functionsCD4 T cell functionCD4 T cell proliferationCD4 T cell subsetsHematopoietic stem cell transplantationPeripheral blood mononuclear cellsNaive T cell proliferationSuppression of TregsGeneration of TregsInflammatory bowel diseaseRegulatory T cellsStem cell transplantationT cell subsetsBlood mononuclear cellsImmune cell defectsAnti-inflammatory macrophagesT cell functionImmune cell functionReal-time polymerase chain reaction
2015
Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells
Sefik E, Geva-Zatorsky N, Oh S, Konnikova L, Zemmour D, McGuire AM, Burzyn D, Ortiz-Lopez A, Lobera M, Yang J, Ghosh S, Earl A, Snapper SB, Jupp R, Kasper D, Mathis D, Benoist C. Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells. Science 2015, 349: 993-997. PMID: 26272906, PMCID: PMC4700932, DOI: 10.1126/science.aaa9420.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacteriaBacteroidetesColitis, UlcerativeColonForkhead Transcription FactorsHomeostasisHumansImmunity, MucosalIntestinal MucosaMice, Inbred C57BLMicrobiotaNuclear Receptor Subfamily 1, Group F, Member 3SymbiosisT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryTh17 CellsTranscription, GeneticTranscriptomeConceptsRegulatory T cellsImmuno-inflammatory responseT helper 17 (Th17) cell differentiationTranscription factor Foxp3Important effector moleculeRegulatory cellsHuman gut microbiotaFactor Foxp3T cellsRelated cell typesGut microbiotaMouse colonRORγSymbiotic membersIntestinal symbiontsFoxp3Tissue homeostasisEffector moleculesCell differentiationCell typesDistinct populationsCellsDifferent outcomesInflammation