2025
A single-cell atlas of circulating immune cells over the first 2 months of age in extremely premature infants
Olaloye O, Gu W, Gehlhaar A, Sabuwala B, Eke C, Li Y, Kehoe T, Farmer R, Gabernet G, Lucas C, Tsang J, Lakhani S, Taylor S, Tseng G, Kleinstein S, Konnikova L. A single-cell atlas of circulating immune cells over the first 2 months of age in extremely premature infants. Science Translational Medicine 2025, 17: eadr0942. PMID: 40043141, DOI: 10.1126/scitranslmed.adr0942.Peer-Reviewed Original ResearchConceptsExtremely premature infantsFull-term infantsT cellsMonths of lifePremature infantsImmune cellsMemory CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cellsMemory-like T cellsAnalysis of immune cellsNaive CD4<sup>+</sup>Peripheral T cell developmentWeeks of gestationCord blood samplesNatural killer cellsT helper 1B cell receptor sequencesT cell developmentCycling T cellsMonths of ageSingle-cell suspensionsAmount of bloodSusceptibility to infectionCD4<sup>+</sup>Killer cellsImmune dysregulation in glycogen storage disease 1b extends beyond neutropenia
Gehlhaar A, Shouval D, Santiago E, Ling G, McCourt B, Werner L, Yerushalmi B, Konnikova L. Immune dysregulation in glycogen storage disease 1b extends beyond neutropenia. Human Immunology 2025, 86: 111268. PMID: 40037121, DOI: 10.1016/j.humimm.2025.111268.Peer-Reviewed Original ResearchGlycogen storage disease type 1bGlycogen storage disease type 1b patientsImpaired immune cell traffickingClassic treatment strategiesUpregulation of CXCR3Effector memory phenotypeT cell populationsNatural killer cellsSystems immunology approachNon-classical monocytesImmune cell traffickingGlycogen storage disease 1bImmune defectsMemory phenotypeMultiple T cell populationsImmune landscapeRecurrent infectionsKiller cellsImmune dysregulationImmune impairmentImmunophenotypic characterizationSLC37A4 geneControl subjectsTreatment strategiesNeutrophil numbersRenalase levels are decreased in maternal blood and placental tissues in pregnancies associated with preterm preeclampsia
Soliman Y, Eke C, Guo X, Wang M, Silva T, DĂ©sir G, Konnikova L. Renalase levels are decreased in maternal blood and placental tissues in pregnancies associated with preterm preeclampsia. Scientific Reports 2025, 15: 6480. PMID: 39987333, PMCID: PMC11846959, DOI: 10.1038/s41598-025-90524-z.Peer-Reviewed Original ResearchConceptsCases of preeclampsiaSerum renalasePreterm casesRenalase levelsPregnancies associated with hypertensionFactors associated with preeclampsiaRisk of eclampsiaPathophysiology of preeclampsiaLevels of renalasePreterm preeclampsiaTerm preeclampsiaMaternal serumMaternal bloodRenalase expressionPlacental villiPreeclampsiaPlacental tissuePretermPlacentaRenalaseMaternal healthPregnancyHypertensionSerumVariable effectsInterleukin-10 production by innate lymphoid cells restricts intestinal inflammation in mice
Li J, Jacobse J, Pilat J, Kaur H, Gu W, Kang S, Rusznak M, Huang H, Barrera J, Oloo P, Roland J, Hawkins C, Pahnke A, Khalil M, Washington M, Wilson K, Williams C, Peebles R, Konnikova L, Choksi Y, Hammer G, Lau K, Goettel J. Interleukin-10 production by innate lymphoid cells restricts intestinal inflammation in mice. Mucosal Immunology 2025 PMID: 39988202, DOI: 10.1016/j.mucimm.2025.02.005.Peer-Reviewed Original ResearchInnate lymphoid cellsIL-10Lymphoid cellsImmune homeostasisInterleukin-10Population of innate lymphoid cellsIntestinal inflammationIntestinal macrophagesIL-10 receptor signalingModel of experimental colitisPromote immune homeostasisInterleukin-10 productionFluorescent protein reporterIL-10 productionIntestinal immune homeostasisCX3CR1-expressing cellsRNA in situ hybridizationCell-specific targetingAdoptive transferSpontaneous colitisProtein reporterIL10 deficiencyReporter miceImmune cellsImmunomodulatory cytokines
2024
4.1 – 00057 Tissue resident memory programs of intestinal CD4+ and CD8+ T cells facilitate HIV-1 persistence
Wei Y, Ma H, Wong M, Konnikova L, Tebas P, Morgenstern R, Papasavvas E, Montaner L, Ho Y. 4.1 – 00057 Tissue resident memory programs of intestinal CD4+ and CD8+ T cells facilitate HIV-1 persistence. Journal Of Virus Eradication 2024, 10: 13. DOI: 10.1016/j.jve.2024.100412.Peer-Reviewed Original ResearchComprehensive evaluation and practical guideline of gating methods for high-dimensional cytometry data: manual gating, unsupervised clustering, and auto-gating
Liu P, Pan Y, Chang H, Wang W, Fang Y, Xue X, Zou J, Toothaker J, Olaloye O, Santiago E, McCourt B, Mitsialis V, Presicce P, Kallapur S, Snapper S, Liu J, Tseng G, Konnikova L, Liu S. Comprehensive evaluation and practical guideline of gating methods for high-dimensional cytometry data: manual gating, unsupervised clustering, and auto-gating. Briefings In Bioinformatics 2024, 26: bbae633. PMID: 39656848, PMCID: PMC11630031, DOI: 10.1093/bib/bbae633.Peer-Reviewed Original ResearchEnhanced placental antibody transfer efficiency with longer interval between maternal RSV vaccination and birth
Jasset O, Lopez Zapana P, Bahadir Z, Shook L, Dennis M, Gilbert E, Liu Z, Yinger R, Bald C, Bradford C, Silfen A, Klein S, Pekosz A, Permar S, Konnikova L, Yonker L, Lauffenburger D, Nelson A, Elovitz M, Edlow A. Enhanced placental antibody transfer efficiency with longer interval between maternal RSV vaccination and birth. American Journal Of Obstetrics And Gynecology 2024 PMID: 39515450, DOI: 10.1016/j.ajog.2024.10.053.Peer-Reviewed Original ResearchMaternal RSV vaccineRespiratory syncytial virusRespiratory syncytial virus vaccineNatural RSV infectionRSV vaccineRSV infectionBinding antibody multiplex assayTiming of maternal vaccinationTransplacental transfer of maternal antibodiesAntibody levelsRespiratory syncytial virus strains A2Vaccine administrationInfant antibody levelsMaternal antibodiesMother to fetusProspective cohort studyTransfer of maternal antibodiesWilcoxon rank sum testWeek windowVaccination timingLevels of IgGRank sum testTransfer of antibodiesMonths of ageGestational ageImmune landscape of oncohistone-mutant gliomas reveals diverse myeloid populations and tumor-promoting function
Andrade A, Annett A, Karimi E, Topouza D, Rezanejad M, Liu Y, McNicholas M, Gonzalez Santiago E, Llivichuzhca-Loja D, Gehlhaar A, Jessa S, De Cola A, Chandarana B, Russo C, Faury D, Danieau G, Puligandla E, Wei Y, Zeinieh M, Wu Q, Hebert S, Juretic N, Nakada E, Krug B, Larouche V, Weil A, Dudley R, Karamchandani J, Agnihotri S, Quail D, Ellezam B, Konnikova L, Walsh L, Pathania M, Kleinman C, Jabado N. Immune landscape of oncohistone-mutant gliomas reveals diverse myeloid populations and tumor-promoting function. Nature Communications 2024, 15: 7769. PMID: 39237515, PMCID: PMC11377583, DOI: 10.1038/s41467-024-52096-w.Peer-Reviewed Original ResearchConceptsMyeloid populationsTumor microenvironmentExpression of immune checkpoint markersImmune checkpoint pathwaysImmune checkpoint markersSyngeneic mouse modelTumor-promoting functionsCheckpoint markersMyeloid infiltrationImmune landscapeImmune infiltrationImmune lineagesMyeloid cellsLymphoid cellsTumor cellsMouse modelTumor formationBenefit of patientsTherapeutic benefitBrain tumorsGliomaTumorDysregulated epigenomeDual inhibitionInfiltrationHuman Milk Supports Robust Intestinal Organoid Growth, Differentiation, and Homeostatic Cytokine Production
Smith L, Santiago E, Eke C, Gu W, Wang W, Llivichuzhca-Loja D, Kehoe T, St Denis K, Strine M, Taylor S, Tseng G, Konnikova L. Human Milk Supports Robust Intestinal Organoid Growth, Differentiation, and Homeostatic Cytokine Production. Gastro Hep Advances 2024, 3: 1030-1042. PMID: 39529649, PMCID: PMC11550179, DOI: 10.1016/j.gastha.2024.07.007.Peer-Reviewed Original ResearchHuman milk supplementationTNF-related apoptosis inducing ligandDonor human milkLevels of leukemia inhibitory factorNecrotizing enterocolitisCytokine productionInflammatory immune signaturesComplications of prematurityHuman milkChromogranin A stainingSevere gastrointestinal complicationsMilk supplementationCell cycle-promoting genesIntestinal organoidsApoptosis inducing ligandIntestinal epithelial proliferationIntestinal epithelial growthGrowth factor analysisCleaved caspase 3Preterm infantsGestational ageLeukemia inhibitory factorImmune signaturesImmune landscapeHydrolyzed formulaPlacenta and Intestinal Injury in Preterm Infants
Garg P, Weitkamp J, McDonald A, Cilvik S, Mir I, Shenberger J, Olaloye O, Konnikova L, Kallapur S, Garg P. Placenta and Intestinal Injury in Preterm Infants. American Journal Of Perinatology 2024, 42: 415-419. PMID: 38889889, PMCID: PMC11724007, DOI: 10.1055/a-2347-4135.Peer-Reviewed Original ResearchNecrotizing enterocolitisIntestinal injuryRisk factors associated with necrotizing enterocolitisDevelopment of necrotizing enterocolitisLow birth weight infantsAssociated with intestinal injuryExposure to inflammationProspective multi-center studyAt-risk infantsHuman clinical studiesMulti-center studyPreterm infantsPlacental pathologyPreterm birthImmunomodulatory treatmentIntrauterine environmentLaboratory predictorsCause of deathClinical outcomesClinical impactClinical studiesPostnatal lifeVulnerable infantsPost pregnancyTriggering inflammationChallenges in IBD Research 2024: Preclinical Human IBD Mechanisms
Ciorba M, Konnikova L, Hirota S, Lucchetta E, Turner J, Slavin A, Johnson K, Condray C, Hong S, Cressall B, Pizarro T, Hurtado-Lorenzo A, Heller C, Moss A, Swantek J, Garrett W. Challenges in IBD Research 2024: Preclinical Human IBD Mechanisms. Inflammatory Bowel Diseases 2024, 30: s5-s18. PMID: 38778627, PMCID: PMC11491665, DOI: 10.1093/ibd/izae081.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseasePreclinical human IBD mechanismsInflammatory bowel disease researchHuman inflammatory bowel diseaseCell statesRisk allelesUnmet medical needExtraintestinal manifestationsPrecision medicineInflammatory bowel disease complicationsPreclinical researchBowel diseasePragmatic clinical researchMultidisciplinary inputBarrier functionDisease researchEnvironmental triggersMedical needClinical researchTranslational scientistsMicrobiomeAllelesEpigeneticsGeneticsRemissionSingle-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“Deficiency in ELF4, X-Linked”: a Monogenic Disease Entity Resembling Behçet’s Syndrome and Inflammatory Bowel Disease
Olyha S, O’Connor S, Kribis M, Bucklin M, Uthaya Kumar D, Tyler P, Alam F, Jones K, Sheikha H, Konnikova L, Lakhani S, Montgomery R, Catanzaro J, Du H, DiGiacomo D, Rothermel H, Moran C, Fiedler K, Warner N, Hoppenreijs E, van der Made C, Hoischen A, Olbrich P, Neth O, RodrĂguez-MartĂnez A, Lucena Soto J, van Rossum A, Dalm V, Muise A, Lucas C. “Deficiency in ELF4, X-Linked”: a Monogenic Disease Entity Resembling Behçet’s Syndrome and Inflammatory Bowel Disease. Journal Of Clinical Immunology 2024, 44: 44. PMID: 38231408, PMCID: PMC10929603, DOI: 10.1007/s10875-023-01610-8.Peer-Reviewed Original ResearchConceptsDEX patientsClass-switched memory B cellsInborn errors of immunityTreated with anti-inflammatory agentsLow natural killerX-linkedMemory B cellsErrors of immunityCohort of patientsIncreased inflammatory cytokinesLoss-of-function variantsHeterogeneous clinical phenotypesInflammatory bowel diseaseTargeted therapeutic interventionsNatural killerAnti-inflammatory agentsAphthous ulcersTherapeutic responseAutoinflammatory syndromeInflammatory markersClinical manifestationsB cellsBehcet's syndromeGastrointestinal symptomsMechanisms of disease
2023
The maternal gut microbiome in pregnancy: implications for the developing immune system
Koren O, Konnikova L, Brodin P, Mysorekar I, Collado M. The maternal gut microbiome in pregnancy: implications for the developing immune system. Nature Reviews Gastroenterology & Hepatology 2023, 21: 35-45. PMID: 38097774, DOI: 10.1038/s41575-023-00864-2.Peer-Reviewed Original ResearchHepatocyte CYR61 polarizes profibrotic macrophages to orchestrate NASH fibrosis
Mooring M, Yeung G, Luukkonen P, Liu S, Akbar M, Zhang G, Balogun O, Yu X, Mo R, Nejak-Bowen K, Poyurovsky M, Booth C, Konnikova L, Shulman G, Yimlamai D. Hepatocyte CYR61 polarizes profibrotic macrophages to orchestrate NASH fibrosis. Science Translational Medicine 2023, 15: eade3157. PMID: 37756381, PMCID: PMC10874639, DOI: 10.1126/scitranslmed.ade3157.Peer-Reviewed Original ResearchConceptsNonalcoholic steatohepatitisLiver inflammationNonalcoholic fatty liver diseaseProgression of NASHCysteine-rich angiogenic inducer 61Fatty liver diseaseLiver-specific knockout miceImproved glucose toleranceType 2 diabetesGlucose toleranceLiver diseaseNASH progressionProfibrotic macrophagesProinflammatory propertiesReduced fibrosisCardiovascular diseaseProfibrotic phenotypeFibrotic developmentKnockout miceNF-ÎşBMetabolic diseasesNASH dietPDGFB expressionFibrosisProfibrotic programSingle-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 ResearchConceptsSingle-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 viewNECPropionate primes the DC pump in neonates
Rice T, Konnikova L. Propionate primes the DC pump in neonates. Immunity 2023, 56: 903-905. PMID: 37163990, DOI: 10.1016/j.immuni.2023.04.006.Peer-Reviewed Original ResearchSingle 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 weekPatientsSurgeryGestationPerforationPrematurityComplicationsDysfunctionMucosaQuestioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies
Kennedy K, de Goffau M, Perez-Muñoz M, Arrieta M, Bäckhed F, Bork P, Braun T, Bushman F, Dore J, de Vos W, Earl A, Eisen J, Elovitz M, Ganal-Vonarburg S, Gänzle M, Garrett W, Hall L, Hornef M, Huttenhower C, Konnikova L, Lebeer S, Macpherson A, Massey R, McHardy A, Koren O, Lawley T, Ley R, O’Mahony L, O’Toole P, Pamer E, Parkhill J, Raes J, Rattei T, Salonen A, Segal E, Segata N, Shanahan F, Sloboda D, Smith G, Sokol H, Spector T, Surette M, Tannock G, Walker A, Yassour M, Walter J. Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies. Nature 2023, 613: 639-649. PMID: 36697862, PMCID: PMC11333990, DOI: 10.1038/s41586-022-05546-8.Peer-Reviewed Original ResearchConceptsMicrobial populationsHuman immune developmentMicrobial ecologyReproductive biologyMicrobial communitiesLow biomass environmentsMicrobial signalsMicrobial studiesDNA sequencingMicrobiome studiesDNA extractionMicrobial analysisClinical microbiologyMechanistic conceptsCautionary exampleImmune developmentRecent studiesHuman fetusesFetal tissuesMammalsGnotobiologyEcologyMicrobiologyFetal microbiomeBiology
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 types
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