2021
Immune-Mediated Reprogramming of Intestinal Stem Cells Drives STAT1-Dependent Myc Expression and Epithelial Regeneration in GI-Gvhd
Takashima S, Sharma R, Egorova A, Kuttiyara J, Ito T, Chang W, Jansen S, Liu C, Lindemans C, Mazutis L, Robine N, Hanash A. Immune-Mediated Reprogramming of Intestinal Stem Cells Drives STAT1-Dependent Myc Expression and Epithelial Regeneration in GI-Gvhd. Blood 2021, 138: 86-86. DOI: 10.1182/blood-2021-152647.Peer-Reviewed Original ResearchIntestinal stem cellsGene set enrichment analysisMYC expressionIFNG treatmentSTAT1-dependent mannerActivating myc expressionDownstream of Wnt signalingInduced epithelial apoptosisInhibitor 10058-F4Intestinal stem cell maintenanceMYC inhibitor 10058-F4Single cell RNA sequencingIFNG signalingIntestinal stem cell populationIntestinal cryptsCell RNA sequencingGene expression profilesCell cycle analysisUpregulated transcription factorsWnt target gene Axin2Myc functionUpregulation of cyclin D1Sequenced cellsMYC pathwayPhenotypic distances
2019
T cell–derived interferon-γ programs stem cell death in immune-mediated intestinal damage
Takashima S, Martin M, Jansen S, Fu Y, Bos J, Chandra D, O'Connor M, Mertelsmann A, Vinci P, Kuttiyara J, Devlin S, Middendorp S, Calafiore M, Egorova A, Kleppe M, Lo Y, Shroyer N, Cheng E, Levine R, Liu C, Kolesnick R, Lindemans C, Hanash A. T cell–derived interferon-γ programs stem cell death in immune-mediated intestinal damage. Science Immunology 2019, 4 PMID: 31811055, PMCID: PMC7239329, DOI: 10.1126/sciimmunol.aay8556.Peer-Reviewed Original ResearchConceptsBone marrow transplantationIntestinal stem cellsDonor T cellsStem cell compartmentT cellsStem cell deathEpithelial culturesAllogeneic bone marrow transplantationDysregulated T cell activationT cell-mediated pathologyInhibition of JAK signalingStem cellsImmune-mediated damageActivated T cellsT cell activationCell compartmentCell deathTissue stem cellsPaneth cell nicheIFNg productionMarrow transplantationIntestinal immunopathologyInterferon-gHealthy miceStem cell colonies
2015
IL-22 Directly Regulates Intestinal Stem Cells, Protecting Epithelium from GvHD and Reducing GvHD Mortality
Lindemans C, Mertelsmann A, O'Connor M, Calafiore M, Dudakov J, Jenq R, Velardi E, Young L, Smith O, Lawrence G, Luo N, Ivanov J, Hua G, Martin L, Liu C, Kolesnick R, van den Brink M, Hanash A. IL-22 Directly Regulates Intestinal Stem Cells, Protecting Epithelium from GvHD and Reducing GvHD Mortality. Transplantation And Cellular Therapy 2015, 21: s58-s59. DOI: 10.1016/j.bbmt.2014.11.058.Peer-Reviewed Original Research
2012
Interleukin-22 Protects Intestinal Stem Cells from Immune-Mediated Tissue Damage and Regulates Sensitivity to Graft versus Host Disease
Hanash A, Dudakov J, Hua G, O’Connor M, Young L, Singer N, West M, Jenq R, Holland A, Kappel L, Ghosh A, Tsai J, Rao U, Yim N, Smith O, Velardi E, Hawryluk E, Murphy G, Liu C, Fouser L, Kolesnick R, Blazar B, van den Brink M. Interleukin-22 Protects Intestinal Stem Cells from Immune-Mediated Tissue Damage and Regulates Sensitivity to Graft versus Host Disease. Immunity 2012, 37: 339-350. PMID: 22921121, PMCID: PMC3477611, DOI: 10.1016/j.immuni.2012.05.028.Peer-Reviewed Original ResearchConceptsIL-23-responsive innate lymphoid cellsIntestinal IL-22IL-22Intestinal stem cellsTissue damageHost diseaseTransplant recipientsIL-22 deficiencyInflammatory intestinal damageDonor immune systemInnate lymphoid cellsBone marrow transplantIL-22 receptorStem cellsILC frequenciesPretransplant conditioningIntestinal damageMarrow transplantCrypt apoptosisLymphoid cellsImmune systemGVHDTissue sensitivityProtective factorsEpithelial integrity
2011
Host-Derived IL-22 Limits Graft Versus Host Disease and Protects the Intestinal Stem Cell Niche
Hanash A, Dudakov J, Hua G, Young L, O'connor M, Jenq R, Holland A, Smith O, Liu C, Fouser L, Kolesnick R, Blazar B, Van Den Brink M. Host-Derived IL-22 Limits Graft Versus Host Disease and Protects the Intestinal Stem Cell Niche. Blood 2011, 118: 309. DOI: 10.1182/blood.v118.21.309.309.Peer-Reviewed Original ResearchInnate lymphoid cellsIL-22 deficiencyDonor immune responsesIL-22R expressionIL-22Post-BMTIntestinal stem cellsIntestinal epitheliumGVHD mortalityKO recipientsHost diseaseClinical GVHDT cellsImmune responseIL-22-producing innate lymphoid cellsGraft Versus Host DiseaseIL-22 KO miceLarge intestineMurine bone marrow transplantationHost hematopoietic cellsTarget of GVHDVersus Host DiseaseIL-22 productionDonor immune systemIL-22 levels