2024
Challenges 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 scientistsMicrobiomeAllelesEpigeneticsGeneticsRemission
2023
Hepatocyte 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 programQuestioning 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
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 responseThe Protective Effects of Calcineurin on Pancreatitis in Mice Depend on the Cellular Source
Wen L, Javed TA, Dobbs AK, Brown R, Niu M, Li L, Khalid A, Barakat M, Xiao X, Yimlamai D, Konnikova L, Yu M, Byersdorfer CA, Husain SZ. The Protective Effects of Calcineurin on Pancreatitis in Mice Depend on the Cellular Source. Gastroenterology 2020, 159: 1036-1050.e8. PMID: 32445858, PMCID: PMC7502475, DOI: 10.1053/j.gastro.2020.05.051.Peer-Reviewed Original ResearchMeSH KeywordsAcinar CellsAcute Lung InjuryAnimalsBone Marrow CellsCalcineurinCalcineurin InhibitorsCalcium-Binding ProteinsCells, CulturedCeruletideCytokinesDisease Models, AnimalFemaleHumansMaleMiceMice, TransgenicMuscle ProteinsNeutrophilsNFATC Transcription FactorsPancreasPancreatitisPrimary Cell CultureConceptsAdministration of caeruleinLocal pancreatic inflammationBiliopancreatic ductPancreas-specific deletionLung inflammationPancreatic inflammationAcute pancreatitisControl miceNeutrophil chemotaxisProtective effectHematopoietic-specific deletionPancreatic acinar cell necrosisPrevention of pancreatitisLevels of cytokinesAcinar cell necrosisSwiss Webster miceActivated T cellsAdeno-associated virus vectorPrimary pancreatic acinar cellsReactive oxygen species productionNFAT-luciferaseSevere pancreatitisCalcineurin inhibitorsNeutrophil expressionPancreatic acinar cells
2019
Low-Dose Interleukin-2 Ameliorates Colitis in a Preclinical Humanized Mouse Model
Goettel JA, Kotlarz D, Emani R, Canavan JB, Konnikova L, Illig D, Frei SM, Field M, Kowalik M, Peng K, Gringauz J, Mitsialis V, Wall SM, Tsou A, Griffith AE, Huang Y, Friedman JR, Towne JE, Plevy SE, Hall A, Snapper SB. Low-Dose Interleukin-2 Ameliorates Colitis in a Preclinical Humanized Mouse Model. Cellular And Molecular Gastroenterology And Hepatology 2019, 8: 193-195. PMID: 31078723, PMCID: PMC6661391, DOI: 10.1016/j.jcmgh.2019.05.001.Peer-Reviewed Original Research
2018
WASP-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
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
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 3SymbiosisTh17 CellsT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryTranscription, 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