2024
Placenta 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 PMID: 38889889, 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 inflammationHuman 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 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 formulaChallenges 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, 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, Gonzalez 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 PMID: 38555026, 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, Rodríguez-Martínez 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-κBMetabolic 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, 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 typesInsulin is expressed by enteroendocrine cells during human fetal development
A E, D L, BT M, K B, L F, X A, F W, K C, L K, S I. Insulin is expressed by enteroendocrine cells during human fetal development. 2022 DOI: 10.1530/ey.19.10.8.Peer-Reviewed Original Research524: PATHOGENIC RIPK1 MUTATIONS CAUSE INFANTILE-ONSET IBD WITH INFLAMMATORY AND FISTULIZING FEATURES
Sultan M, Wilschanski M, Millman P, McCourt B, Kol N, Lev A, Matar M, Barel O, Shamir R, Konnikova L, Somech R, Shouval D. 524: PATHOGENIC RIPK1 MUTATIONS CAUSE INFANTILE-ONSET IBD WITH INFLAMMATORY AND FISTULIZING FEATURES. Gastroenterology 2022, 162: s-121-s-122. DOI: 10.1016/s0016-5085(22)60296-8.Peer-Reviewed Original ResearchRenalase and its receptor, PMCA4b, are expressed in the placenta throughout the human gestation
Wang M, Silva T, Toothaker JM, McCourt BT, Shugrue C, Desir G, Gorelick F, Konnikova L. Renalase and its receptor, PMCA4b, are expressed in the placenta throughout the human gestation. Scientific Reports 2022, 12: 4953. PMID: 35322081, PMCID: PMC8943056, DOI: 10.1038/s41598-022-08817-6.Peer-Reviewed Original ResearchConceptsPlacental tissuePlacental villiHofbauer cellsPlacental developmentEndogenous productionAnti-inflammatory milieuPotential roleHuman placental tissueFull-term placentaPlacental factorsFetal interfaceDecidual samplesPlacental functionChorionic plateImmunoreactive cellsPlacental samplesHuman gestationRenalaseBulk RNA sequencingHuman placentaPlacentaQuantification of immunohistochemistryProtein levelsTrophoblastTransmission of nutrientsInsights into the Role of Commensal-Specific T Cells in Intestinal Inflammation
Gehlhaar A, Inala A, Llivichuzhca-Loja D, Silva TN, Adegboye CY, O’Connell A, Konnikova L. Insights into the Role of Commensal-Specific T Cells in Intestinal Inflammation. Journal Of Inflammation Research 2022, 15: 1873-1887. PMID: 35342295, PMCID: PMC8943607, DOI: 10.2147/jir.s288288.Peer-Reviewed Original ResearchT cellsIntestinal inflammationIntestinal inflammatory responseDamaging autoimmune responsesTrillions of microorganismsImmunological balanceAutoimmune responseImmune homeostasisInflammatory responseImmune systemMucosal interfaceBarrier sitesHuman intestineInflammationIntestinePrevious evidenceCellsCD8CD4ThymusResponseImmune 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
2021
CD16+CD163+ monocytes traffic to sites of inflammation during necrotizing enterocolitis in premature infants
Olaloye OO, Liu P, Toothaker JM, McCourt BT, McCourt CC, Xiao J, Prochaska E, Shaffer S, Werner L, Faculty U, Faculty U, Gringauz J, Good M, Goldsmith JD, An X, Wang F, Snapper SB, Shouval D, Chen K, Tseng G, Konnikova L. CD16+CD163+ monocytes traffic to sites of inflammation during necrotizing enterocolitis in premature infants. Journal Of Experimental Medicine 2021, 218: e20200344. PMID: 34269788, PMCID: PMC8289692, DOI: 10.1084/jem.20200344.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, MyelomonocyticBlood VesselsCase-Control StudiesChemotaxisEnterocolitis, NecrotizingGastric MucosaGPI-Linked ProteinsHumansInfantInfant, NewbornIntestine, SmallMonocytesNeutropeniaNeutrophilsPhagocytosisReactive Oxygen SpeciesReceptors, Cell SurfaceReceptors, IgGSequence Analysis, RNASingle-Cell AnalysisConceptsSurgical NECCirculation of infantsDistinct neutrophil phenotypesSevere gastrointestinal complicationsAreas of inflammationSites of inflammationMonocyte trafficGastrointestinal complicationsPremature infantsNeutrophil phenotypeSevere inflammationInflammatory genesPotential biomarkersSingle-cell RNA sequencingOxygen species generationInflammationNovel subtypeBlood vesselsMass cytometryNECEnterocolitisMucosaInfantsMϕsSpecies generationSerum Analyte Profiles Associated With Crohn’s Disease and Disease Location
Boucher G, Paradis A, Chabot-Roy G, Coderre L, Hillhouse E, Bitton A, Rosiers C, Levings M, Schumm L, Lazarev M, Brant S, Duerr R, McGovern D, Silverberg M, Cho J, Lesage S, Rioux J, Bitton A, Boucher G, Charron G, Rosiers C, Forest A, Goyette P, Ivinson S, Joseph L, Kohen R, Lachaine J, Lesage S, Levings M, Rioux J, Thompson-Legault J, Vachon L, Veilleux S, White-Guay B, Bajpai M, Birch S, Bitton A, Borowski K, Botwin G, Boucher G, Brant S, Chen W, Cho J, Cordero R, Côté-Daigneault J, Daly M, Datta L, Duerr R, Filice M, Fleshner P, Gettler K, Giri M, Goyette P, Hao K, Haritunians T, Itan Y, Johnston E, Konnikova L, Landers C, Lazarev M, Li D, McGovern D, Mengesha E, Merad M, Miladinova V, Nayeri S, Proksell S, Raquel M, Rioux J, Rymaszewski K, Sabic K, Sands B, Schumm L, Schwartz M, Silverberg M, Simpson C, Stempak J, Stevens C, Targan S, Xavier R. Serum Analyte Profiles Associated With Crohn’s Disease and Disease Location. Inflammatory Bowel Diseases 2021, 28: 9-20. PMID: 34106269, PMCID: PMC8730700, DOI: 10.1093/ibd/izab123.Peer-Reviewed Original ResearchConceptsCrohn's diseaseDisease locationCD patientsIL-6 beingColonic Crohn's diseaseInterleukin IL-6IL-12p70Chronic inflammationColorectal diseaseIL-6Inflammatory processHealthy controlsColorectal regionIntestinal microbiotaClinical observationsEpithelial barrierImmune systemPatientsSerum analytesEndothelial systemDiseaseSerum samplesGrowth factorMultiple cell typesDigestive tract