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, 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 scientistsMicrobiomeAllelesEpigeneticsGeneticsRemission
2020
An RTEL1 Mutation Links to Infantile-Onset Ulcerative Colitis and Severe Immunodeficiency
Ziv A, Werner L, Konnikova L, Awad A, Jeske T, Hastreiter M, Mitsialis V, Stauber T, Wall S, Kotlarz D, Klein C, Snapper SB, Tzfati Y, Weiss B, Somech R, Shouval DS. An RTEL1 Mutation Links to Infantile-Onset Ulcerative Colitis and Severe Immunodeficiency. Journal Of Clinical Immunology 2020, 40: 1010-1019. PMID: 32710398, DOI: 10.1007/s10875-020-00829-z.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseasePeripheral blood mononuclear cellsUlcerative colitisInfantile-onset inflammatory bowel diseasePatients' peripheral blood mononuclear cellsInnate immune subsetsPneumocystis jiroveci pneumoniaUnique clinical manifestationsBlood mononuclear cellsNaïve T cellsMass cytometry analysisHoyeraal-Hreidarsson syndromeAshkenazi Jewish patientsWhole-exome sequencingDifferent monogenic disordersImmunologic alterationsJiroveci pneumoniaBowel diseaseImmune subsetsImmunological alterationsImmune landscapeCarriage rateClinical manifestationsMononuclear cellsControl subjects
2018
Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy
Kotlarz D, Marquardt B, Barøy T, Lee WS, Konnikova L, Hollizeck S, Magg T, Lehle AS, Walz C, Borggraefe I, Hauck F, Bufler P, Conca R, Wall SM, Schumacher EM, Misceo D, Frengen E, Bentsen BS, Uhlig HH, Hopfner KP, Muise AM, Snapper SB, Strømme P, Klein C. Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy. Nature Genetics 2018, 50: 344-348. PMID: 29483653, PMCID: PMC6309869, DOI: 10.1038/s41588-018-0063-6.Peer-Reviewed Original ResearchConceptsInfantile inflammatory bowel diseaseInflammatory bowel diseaseTGF-β1Bowel diseaseSevere inflammatory bowel diseaseCentral nervous system diseaseNervous system diseasesRole of TGFPosterior leukoencephalopathyIntestinal immunityBrain atrophySystem diseasesTGFB1 geneBiallelic lossImpaired secretionGrowth factorTGF-β familyDiseaseTGF-β1 deficiencyNonredundant roleFunction mutationsPrototypic memberLeukoencephalopathyAtrophyEpilepsy
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