2024
Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties.
Shin J, Park J, Lim J, Jeong J, Dinesh R, Maher S, Kim J, Park S, Hong J, Wysolmerski J, Choi J, Bothwell A. Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties. ELife 2024, 13 PMID: 39535280, PMCID: PMC11560131, DOI: 10.7554/elife.97279.Peer-Reviewed Original ResearchConceptsCancer cellsDickkopf-2Analysis of transcriptomeGeneration of cancer cellsPositive cancer cellsStem cell niche factorsColon cancer cellsPaneth cell differentiationHepatocyte nuclear factor 4 alphaLysozyme positive cellsChromatin accessibilityHNF4A proteinSingle-cell RNA sequencing analysisCell propertiesPaneth cell markersSequence analysisChromatin immunoprecipitationPromoter regionTranscription factorsTranscriptome analysisColon cancerColon cancer metastasisReduction of liver metastasisDownstream targetsCell differentiation
2018
Regulation of human T cell responses by dNP2-ctCTLA-4 inhibits human skin and microvessel graft rejection
Lim S, Kirkiles-Smith NC, Pober JS, Bothwell ALM, Choi JM. Regulation of human T cell responses by dNP2-ctCTLA-4 inhibits human skin and microvessel graft rejection. Biomaterials 2018, 183: 128-138. PMID: 30165256, PMCID: PMC6141312, DOI: 10.1016/j.biomaterials.2018.08.049.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell ProliferationCell-Penetrating PeptidesCTLA-4 AntigenCytokinesEndothelial CellsFemaleGraft RejectionHuman Umbilical Vein Endothelial CellsHumansLymphocyte ActivationMice, Inbred BALB CMice, KnockoutMice, SCIDMicrovesselsReceptors, ChemokineSkinSkin TransplantationT-LymphocytesConceptsT cell responsesHuman T cell responsesT cell infiltrationHuman T cellsT cellsCell responsesGraft rejectionCell infiltrationSCID/beige miceCell-permeable peptideBlood cytokine levelsT cell alloresponsesCD8 T cellsChemokine receptor expressionGranzyme B expressionAlloreactive T cellsSignificant side effectsDouble knockout miceHuman T cell activationBcl-2-transduced human umbilical vein endothelial cellsT cell activationHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsSystemic immunosuppressantsAllograft rejection
2017
Membrane‐bound Dickkopf‐1 in Foxp3+ regulatory T cells suppresses T‐cell‐mediated autoimmune colitis
Chae W, Park J, Henegariu O, Yilmaz S, Hao L, Bothwell ALM. Membrane‐bound Dickkopf‐1 in Foxp3+ regulatory T cells suppresses T‐cell‐mediated autoimmune colitis. Immunology 2017, 152: 265-275. PMID: 28556921, PMCID: PMC5588763, DOI: 10.1111/imm.12766.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAutoimmune DiseasesAutoimmunityCell MembraneCell ProliferationCHO CellsColitisColonCricetulusDisease Models, AnimalDNA-Binding ProteinsForkhead Transcription FactorsGenetic Predisposition to DiseaseIntercellular Signaling Peptides and ProteinsLymphocyte ActivationMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein KinasesPhenotypeSelf ToleranceSignal TransductionTime FactorsT-Lymphocytes, RegulatoryTransfectionConceptsRegulatory T cellsTreg cellsDKK-1 expressionAutoimmune colitisDickkopf-1T cellsT cell-mediated toleranceEffector CD4 T cellsCD4 T cellsInduction of toleranceT cell proliferationT cell receptor stimulationNovel TregColitis modelImmunological homeostasisImmunological toleranceFoxp3Receptor stimulationCanonical Wnt pathwayColitisFunctional inhibitionMonoclonal antibodiesDe novo protein synthesisProtein kinase pathwaySuppressor functionStat6 Promotes Intestinal Tumorigenesis in a Mouse Model of Adenomatous Polyposis by Expansion of MDSCs and Inhibition of Cytotoxic CD8 Response
Jayakumar A, Bothwell ALM. Stat6 Promotes Intestinal Tumorigenesis in a Mouse Model of Adenomatous Polyposis by Expansion of MDSCs and Inhibition of Cytotoxic CD8 Response. Neoplasia 2017, 19: 595-605. PMID: 28654863, PMCID: PMC5487300, DOI: 10.1016/j.neo.2017.04.006.Peer-Reviewed Original ResearchMeSH KeywordsAdenomatous Polyposis ColiAnimalsBecaplerminBiomarkersCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell Transformation, NeoplasticCytotoxicity, ImmunologicDisease Models, AnimalDisease ProgressionGene DeletionGene ExpressionInterleukin-4Intestinal MucosaIntestine, SmallMiceMice, KnockoutMyeloid-Derived Suppressor CellsProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins c-sisSTAT6 Transcription FactorConceptsIntestinal tumorigenesisIL-4-induced STAT6Tumor-promoting growth factorsAntitumor T-cell responsesHuman colorectal cancer tissuesMore CD8 cellsPD-1 expressionEpithelial cellsExpansion of MDSCsT cell responsesIL-4 expressionCell proliferationColorectal cancer tissuesPlatelet-derived growth factor-BBIntestinal tumor progressionIntestinal epithelial cellsGrowth factor-BBColon cancer cell linesCD8 responsesPolyp progressionStrong CD8Cancer cell linesCD4 cellsCD8 cellsImmunosuppressive mediators
2016
Gender-specific differences in PPARγ regulation of follicular helper T cell responses with estrogen
Park HJ, Park HS, Lee JU, Bothwell AL, Choi JM. Gender-specific differences in PPARγ regulation of follicular helper T cell responses with estrogen. Scientific Reports 2016, 6: 28495. PMID: 27335315, PMCID: PMC4917844, DOI: 10.1038/srep28495.Peer-Reviewed Original ResearchConceptsFollicular helper T cell responsesHelper T cell responsesT cell responsesCell responsesTfh cellsT cellsGC responseMale T cellsPeroxisome proliferator-activated receptor gammaTfh cell responsesEffector T cellsPPARγ agonist pioglitazoneProliferator-activated receptor gammaT cell regulationWild-type miceRole of PPARγGerminal center B cellsT cell activationGender-specific differencesTfh responsesAgonist pioglitazoneAutoimmune diseasesMenstrual cycleFemale miceMale mice
2011
IL-17F deficiency inhibits small intestinal tumorigenesis in ApcMin/+ mice
Chae WJ, Bothwell AL. IL-17F deficiency inhibits small intestinal tumorigenesis in ApcMin/+ mice. Biochemical And Biophysical Research Communications 2011, 414: 31-36. PMID: 21939640, DOI: 10.1016/j.bbrc.2011.09.016.Peer-Reviewed Original ResearchConceptsIL-17FSpontaneous intestinal tumorigenesisIntestinal tumorigenesisLamina propriaCD4 T cellsImmune cell infiltrationCOX-2 expressionSmall intestinal tumorigenesisIL-17IL-17AIL-17A.IL-17F.Thymic atrophyIL-1βCell infiltrationT cellsGut homeostasisSmall intestineMiceSignificant decreaseC expressionTumorigenesisPropriaIntestineAblation
2010
Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation
Choi JM, Shin JH, Sohn MH, Harding MJ, Park JH, Tobiasova Z, Kim DY, Maher SE, Chae WJ, Park SH, Lee CG, Lee SK, Bothwell AL. Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 18575-18580. PMID: 20937878, PMCID: PMC2972952, DOI: 10.1073/pnas.1000400107.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAsthmaAutoimmune DiseasesCell Membrane PermeabilityDisease Models, AnimalFemaleForkhead Transcription FactorsHumansInflammatory Bowel DiseasesLymphocyte ActivationMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, Mutant StrainsRecombinant Fusion ProteinsT-Lymphocytes, RegulatoryConceptsAllergic airway inflammationT cellsAirway inflammationAllergic diseasesFOXP3 proteinOvalbumin-induced allergic airway inflammationWild-type CD4 T cellsAllergic disease modelsDevelopment of colitisInflammatory bowel diseaseRegulatory T cellsCD4 T cellsInflammatory immune responseT cell activationFoxP3 transductionBowel diseaseScurfy miceTreg functionAutoimmune diseasesAutoimmune symptomsIntranasal deliveryTherapeutic effectImmune responseSystemic deliveryClinical potentialAblation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis
Chae WJ, Gibson TF, Zelterman D, Hao L, Henegariu O, Bothwell AL. Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 5540-5544. PMID: 20212110, PMCID: PMC2851824, DOI: 10.1073/pnas.0912675107.Peer-Reviewed Original ResearchConceptsCD4 T cellsSpontaneous intestinal tumorigenesisIL-17AT cellsIntestinal tumorigenesisRegulatory T cell-mediated suppressionEffector CD4 T cellsT cell-mediated suppressionEndogenous IL-17ACell-mediated suppressionInfiltration of lymphocytesIntestinal epithelial cellsHyperproliferative potentialImmunological abnormalitiesAdoptive transferIL-10Proinflammatory mediatorsThymic atrophyInflammatory cytokinesImmunodeficient miceIntestinal architectureHeterozygote mutationsAltered functionMiceTumor development
2009
Transforming growth factor β is dispensable for the molecular orchestration of Th17 cell differentiation
Das J, Ren G, Zhang L, Roberts AI, Zhao X, Bothwell AL, Van Kaer L, Shi Y, Das G. Transforming growth factor β is dispensable for the molecular orchestration of Th17 cell differentiation. Journal Of Experimental Medicine 2009, 206: 2407-2416. PMID: 19808254, PMCID: PMC2768861, DOI: 10.1084/jem.20082286.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCytokinesEncephalomyelitis, Autoimmune, ExperimentalGATA3 Transcription FactorInterleukin-6Lymphocyte ActivationMiceMice, KnockoutSTAT4 Transcription FactorSTAT6 Transcription FactorT-Box Domain ProteinsTh1 CellsTh2 CellsT-Lymphocytes, Helper-InducerTransforming Growth Factor betaConceptsTh17 cell differentiationTh17 cellsIL-6Wild-type BALB/c miceBALB/c miceTh17-specific transcription factorsExperimental autoimmune encephalomyelitisT helper cellsCell differentiationGrowth factor betaTh2 cell differentiationGrowth factor βC-STATAutoimmune encephalomyelitisAntiinflammatory cytokinesAutoimmune disordersProinflammatory cytokinesHelper cellsBeta antibodyC miceTh2 cellsFactor betaGATA-3CytokinesMiceComparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/γc−/−, Balb/c-Rag1−/−γc−/−, and C.B-17-scid/bg immunodeficient mice
Lepus CM, Gibson TF, Gerber SA, Kawikova I, Szczepanik M, Hossain J, Ablamunits V, Kirkiles-Smith N, Herold KC, Donis RO, Bothwell AL, Pober JS, Harding MJ. Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/γc−/−, Balb/c-Rag1−/−γc−/−, and C.B-17-scid/bg immunodeficient mice. Human Immunology 2009, 70: 790-802. PMID: 19524633, PMCID: PMC2949440, DOI: 10.1016/j.humimm.2009.06.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFetal BloodGranulocyte Colony-Stimulating FactorHematopoietic Stem Cell MobilizationHematopoietic Stem Cell TransplantationHematopoietic Stem CellsHemocyaninsHumansHypersensitivity, DelayedImmunoglobulinsInfluenza A Virus, H5N1 SubtypeLiverLymph NodesLymphocyte SubsetsMiceMice, Inbred BALB CMice, Inbred NODMice, KnockoutMice, SCIDRadiation DosageSpleenThymus GlandWhole-Body IrradiationConceptsNOD-scid/Umbilical cord bloodBALB/cHuman fetal liverCord bloodUCB-HSCImmunodeficient miceSecond trimester human fetal liverHematopoietic stem cell preparationsFetal liverTotal human immunoglobulinWhite pulp expansionHumanized mouse modelHematopoietic stem cell engraftmentHuman immune responseHuman immune cellsStem cell engraftmentHuman immune systemHuman T cellsStem cell preparationsDendritic cellsAntigenic challengeDependent antigenPeripheral bloodImmune cells
2006
Natural killer T cells and CD8+ T cells are dispensable for T cell–dependent allergic airway inflammation
Das J, Eynott P, Jupp R, Bothwell A, Van Kaer L, Shi Y, Das G. Natural killer T cells and CD8+ T cells are dispensable for T cell–dependent allergic airway inflammation. Nature Medicine 2006, 12: 1345-1346. PMID: 17151684, DOI: 10.1038/nm1206-1345.Peer-Reviewed Original ResearchPivotal roles of CD8+ T cells restricted by MHC class I–like molecules in autoimmune diseases
Das G, Das J, Eynott P, Zhang Y, Bothwell AL, Van Kaer L, Shi Y. Pivotal roles of CD8+ T cells restricted by MHC class I–like molecules in autoimmune diseases. Journal Of Experimental Medicine 2006, 203: 2603-2611. PMID: 17088432, PMCID: PMC2118151, DOI: 10.1084/jem.20060936.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoimmune DiseasesBeta 2-MicroglobulinCD8-Positive T-LymphocytesCell SurvivalFemaleH-2 AntigensHistocompatibility Antigen H-2DHistocompatibility Antigens Class IIInflammatory Bowel DiseasesIslets of LangerhansLymphoproliferative DisordersMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicNuclear ProteinsTrans-ActivatorsConceptsInnate-like lymphocytesInflammatory bowel diseaseMHC class IT cellsAutoimmune diseasesClass IMajor histocompatibility complex class IaLike moleculesClass II moleculesAdoptive transferBowel diseaseAutoimmune disordersLymphoproliferative syndromeImmunoregulatory functionsAdaptive immunityCD8Class IaDiseaseMiceInsulitisAutoimmunityPivotal roleCellsLymphocytesSyndrome
2004
Pax5-Deficient Mice Exhibit Early Onset Osteopenia with Increased Osteoclast Progenitors
Horowitz MC, Xi Y, Pflugh DL, Hesslein DG, Schatz DG, Lorenzo JA, Bothwell AL. Pax5-Deficient Mice Exhibit Early Onset Osteopenia with Increased Osteoclast Progenitors. The Journal Of Immunology 2004, 173: 6583-6591. PMID: 15557148, DOI: 10.4049/jimmunol.173.11.6583.Peer-Reviewed Original ResearchConceptsNumber of osteoclastsSpleen cellsB cellsOsteoclast developmentB cell-deficient miceCell-deficient miceControl spleen cellsB lymphocyte lineage cellsBone marrow cellsB-cell lineagePro-B cell stageMonocyte phenotypeBone massOsteoclast precursorsMice exhibitOsteoclast progenitorsMarrow cellsGrowth factorMiceOsteoclastsLineage cellsOsteopeniaCell lineagesCellsAdherent cells
2003
Pax5 is required for recombination of transcribed, acetylated, 5′ IgH V gene segments
Hesslein DG, Pflugh DL, Chowdhury D, Bothwell AL, Sen R, Schatz DG. Pax5 is required for recombination of transcribed, acetylated, 5′ IgH V gene segments. Genes & Development 2003, 17: 37-42. PMID: 12514097, PMCID: PMC195966, DOI: 10.1101/gad.1031403.Peer-Reviewed Original ResearchAcetylationAllelesAnimalsB-LymphocytesChromatinDNA NucleotidyltransferasesDNA-Binding ProteinsGene Rearrangement, B-Lymphocyte, Heavy ChainGenes, ImmunoglobulinGenes, RAG-1HistonesHomeodomain ProteinsImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionMiceMice, Inbred C57BLMice, KnockoutPAX5 Transcription FactorTranscription FactorsTranscription, GeneticVDJ Recombinases