2024
DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells
Ren X, Liu Q, Zhou P, Zhou T, Wang D, Mei Q, Flavell R, Liu Z, Li M, Pan W, Zhu S. DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells. Nature Communications 2024, 15: 3080. PMID: 38594251, PMCID: PMC11004185, DOI: 10.1038/s41467-024-47235-2.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseIntestinal stem cellsIntestinal epithelial cellsEpithelial homeostasisSusceptibility to experimental colitisIncreased susceptibility to experimental colitisImpaired ISC functionStem cellsEpithelial barrier dysfunctionGenomic instabilityInflammatory bowel disease patientsPathogenesis of inflammatory bowel diseaseR-loop-mediated genome instabilityHallmarks of inflammatory bowel diseaseContinuous self-renewalBarrier dysfunctionExperimental colitisCrypt destructionEpithelial cellsInflammatory responseSelf-renewalBowel diseaseRisk factorsIntestinal epitheliumProtein levels
2023
Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine
He K, Wan T, Wang D, Hu J, Zhou T, Tao W, Wei Z, Lu Q, Zhou R, Tian Z, Flavell R, Zhu S. Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine. Cell 2023, 186: 3033-3048.e20. PMID: 37327784, DOI: 10.1016/j.cell.2023.05.027.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsCleavage fragmentsSmall intestineCaspase-3/7 inhibitorRegulatory hubTolerance phenotypeN-terminal fragmentHost cellsDifferential cleavageCaspase-3/7Upper small intestineTranscription of CIITAGasdermin DEpithelial cellsMHCII deficiencyMHCII inductionDietary antigensTr1 cellsImmune toleranceProtective immunityFood toleranceForeign antigensMHCII moleculesMiceCells
2011
NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis
Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA, Booth CJ, Peaper DR, Bertin J, Eisenbarth SC, Gordon JI, Flavell RA. NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis. Cell 2011, 145: 745-757. PMID: 21565393, PMCID: PMC3140910, DOI: 10.1016/j.cell.2011.04.022.Peer-Reviewed Original ResearchConceptsDextran sodium sulfateDamage-associated molecular patternsIL-18 levelsInflammatory cell recruitmentInflammasome-deficient miceWild-type miceColonic microbial ecologyMouse colonic epithelial cellsColonic epithelial cellsColitogenic activityDSS colitisHuman IBDChemical colitisIL-18Antibiotic treatmentInflammasome pathwayNLRP6 inflammasomeCell recruitmentIntestinal hyperplasiaColitisCaspase-1Fecal microbiotaMolecular patternsEpithelial cellsExacerbation
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