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
2019
A Unique Presentation of Infantile-Onset Colitis and Eosinophilic Disease without Recurrent Infections Resulting from a Novel Homozygous CARMIL2 Variant
Kurolap A, Eshach Adiv O, Konnikova L, Werner L, Gonzaga-Jauregui C, Steinberg M, Mitsialis V, Mory A, Nunberg MY, Wall S, Shaoul R, Overton JD, Shuldiner A, Zohar Y, Paperna T, Snapper S, Shouval D, Baris Feldman H. A Unique Presentation of Infantile-Onset Colitis and Eosinophilic Disease without Recurrent Infections Resulting from a Novel Homozygous CARMIL2 Variant. Journal Of Clinical Immunology 2019, 39: 430-439. PMID: 31079270, DOI: 10.1007/s10875-019-00631-6.Peer-Reviewed Original ResearchMeSH KeywordsAge of OnsetAmino Acid SequenceChildChild, PreschoolColitisDNA Mutational AnalysisEnteritisEosinophiliaExome SequencingGastritisGenetic Association StudiesGenetic Predisposition to DiseaseHomozygoteHumansImmunohistochemistryImmunophenotypingMaleMicrofilament ProteinsModels, MolecularMutationPhenotypeStructure-Activity RelationshipConceptsWhole-exome sequencingImmunological workupWestern blotRecurrent infectionsGastrointestinal diseasesCyTOF analysisRegulatory T cell frequencyEosinophilic gastrointestinal diseasesEosinophilic gastrointestinal disordersT cell frequenciesUlcerative colitis patientsAdaptive immune cellsEvidence of recurrentSigns of immunodeficiencyT cell proliferationT-cell studiesColitis patientsChronic diarrheaImmunodeficiency syndromeTreg generationGastrointestinal disordersImmunological phenotypeImmune populationsImmune cellsSevere infectionsLow-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