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
2019
Ripk3-induced inflammation by I-MDSCs promotes intestinal tumors
Jayakumar A, Bothwell ALM. Ripk3-induced inflammation by I-MDSCs promotes intestinal tumors. Cancer Research 2019, 79: canres.2153.2018. PMID: 30786994, PMCID: PMC7395226, DOI: 10.1158/0008-5472.can-18-2153.Peer-Reviewed Original ResearchConceptsReceptor-interacting protein kinase 3I-MDSCsIntestinal tumorsIntestinal tumor modelTumor modelColorectal cancerT cellsKey inflammatory mechanismsAntitumor T cellsTransplantable tumor modelsPotential therapeutic targetPossible therapeutic interventionsI-MDSCMDSC subsetsInflammatory mechanismsMDSC functionSuppressor cellsTumor sizeInflammatory cytokinesMC38 tumorsCytokine synthesisMonocytic markersTherapeutic targetTumorigenic factorsTherapeutic interventions
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 function
2016
Sex-Based Selectivity of PPARγ Regulation in Th1, Th2, and Th17 Differentiation
Park HJ, Park HS, Lee JU, Bothwell AL, Choi JM. Sex-Based Selectivity of PPARγ Regulation in Th1, Th2, and Th17 Differentiation. International Journal Of Molecular Sciences 2016, 17: 1347. PMID: 27548145, PMCID: PMC5000743, DOI: 10.3390/ijms17081347.Peer-Reviewed Original ResearchConceptsEffector T cell differentiationT cellsT cell differentiationAdaptive immunityFemale T cellsMale T cellsPeroxisome proliferator-activated receptor gammaIL-17 productionDifferentiation of Th1PPARγ agonist pioglitazoneProliferator-activated receptor gammaNaïve T cellsSplenic T cellsMouse splenic T cellsImportant immune regulatorPioglitazone treatmentTfh responsesTh17 cellsAgonist pioglitazoneTreg functionAutoimmune diseasesEstrogen exposureImmune regulatorsCell differentiationTh1The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation
Chae WJ, Ehrlich AK, Chan PY, Teixeira AM, Henegariu O, Hao L, Shin JH, Park JH, Tang WH, Kim ST, Maher SE, Goldsmith-Pestana K, Shan P, Hwa J, Lee PJ, Krause DS, Rothlin CV, McMahon-Pratt D, Bothwell AL. The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation. Immunity 2016, 44: 246-258. PMID: 26872695, PMCID: PMC4758884, DOI: 10.1016/j.immuni.2016.01.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, DermatophagoidesAntigens, ProtozoanAsthmaBlood PlateletsCell DifferentiationCells, CulturedCytokinesExtracellular Signal-Regulated MAP KinasesGene Expression RegulationHumansInflammationIntercellular Signaling Peptides and ProteinsLeishmania majorLeishmaniasis, CutaneousMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicModels, AnimalPyroglyphidaeSignal TransductionTh2 CellsTOR Serine-Threonine KinasesWnt ProteinsConceptsCell-mediated inflammationTh2 cell cytokine productionCell cytokine productionLeukocyte-platelet aggregatesLeukocyte infiltrationDkk-1Cytokine productionT helper 2 cellsLeishmania major infectionHouse dust miteTranscription factor c-MafAllergen challengeMajor infectionDust miteImmune responseDickkopf-1Parasitic infectionsGATA-3Pathological roleFunctional inhibitionInflammationC-MafP38 MAPKInfiltrationInfection
2015
dNP2 is a blood–brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis
Lim S, Kim WJ, Kim YH, Lee S, Koo JH, Lee JA, Yoon H, Kim DH, Park HJ, Kim HM, Lee HG, Yun Kim J, Lee JU, Hun Shin J, Kyun Kim L, Doh J, Kim H, Lee SK, Bothwell AL, Suh M, Choi JM. dNP2 is a blood–brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis. Nature Communications 2015, 6: 8244. PMID: 26372309, PMCID: PMC4579786, DOI: 10.1038/ncomms9244.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisMultiple sclerosisT cellsAutoimmune encephalomyelitisCytotoxic T-lymphocyte antigen-4T-lymphocyte antigen-4T helper 17 (Th17) cellsCNS inflammatory diseasesTherapeutic mouse modelsEffector T cellsHelper 17 cellsT helper 1Blood-brain barrierCentral nervous systemHuman T cellsHelper 1Antigen-4Inflammatory diseasesMouse modelNervous systemCurrent drugsResident cellsBrain tissueEffective agentCell-permeable peptide
2014
Mutation of POLB Causes Lupus in Mice
Senejani AG, Liu Y, Kidane D, Maher SE, Zeiss CJ, Park HJ, Kashgarian M, McNiff JM, Zelterman D, Bothwell AL, Sweasy JB. Mutation of POLB Causes Lupus in Mice. Cell Reports 2014, 6: 1-8. PMID: 24388753, PMCID: PMC3916967, DOI: 10.1016/j.celrep.2013.12.017.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusLupus-like diseaseLupus erythematosusAutoimmune pathologyMouse modelGenome-wide association studiesPol β activityDecreased expressionMutant miceUnderlying causeMicePrevious genome-wide association studyΒ activityDNA polymerase activityReplication studyExcision repair pathwayImmune diversitySomatic hypermutationBase excision repair pathwayAssociation studiesErythematosusLupusPolymerase activityExpressionKey enzyme
2013
An electrospun scaffold integrating nucleic acid delivery for treatment of full-thickness wounds
Kobsa S, Kristofik NJ, Sawyer AJ, Bothwell AL, Kyriakides TR, Saltzman WM. An electrospun scaffold integrating nucleic acid delivery for treatment of full-thickness wounds. Biomaterials 2013, 34: 3891-3901. PMID: 23453058, PMCID: PMC3625647, DOI: 10.1016/j.biomaterials.2013.02.016.Peer-Reviewed Original Research
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
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
Receptor Activator of NF-κB Ligand Stimulates Recruitment of SHP-1 to the Complex Containing TNFR-Associated Factor 6 That Regulates Osteoclastogenesis
Zhang Z, Jimi E, Bothwell AL. Receptor Activator of NF-κB Ligand Stimulates Recruitment of SHP-1 to the Complex Containing TNFR-Associated Factor 6 That Regulates Osteoclastogenesis. The Journal Of Immunology 2003, 171: 3620-3626. PMID: 14500659, DOI: 10.4049/jimmunol.171.7.3620.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell DifferentiationCell LineCysteineGenetic VectorsGlycoproteinsIntracellular Signaling Peptides and ProteinsLigandsMacrophagesMembrane GlycoproteinsMiceMice, Inbred C57BLMice, Mutant StrainsNF-kappa BOsteoclastsOsteoprotegerinPhosphatidylinositol 3-KinasesPhosphorylationProtein Phosphatase 1Protein Serine-Threonine KinasesProtein SubunitsProtein TransportProtein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesProteinsProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRANK LigandReceptor Activator of Nuclear Factor-kappa BReceptors, Cytoplasmic and NuclearReceptors, Tumor Necrosis FactorRetroviridaeSerineSrc Homology DomainsTNF Receptor-Associated Factor 6Transduction, GeneticTyrosineUp-RegulationConceptsSrc homology 2 domain-containing phosphatase 1Mitogen-activated protein kinaseExpression of SHPProtein kinaseBone marrow macrophagesSrc homology 2 domainTyrosine phosphatase SHP-1P38 mitogen-activated protein kinaseExtracellular signal-regulated kinaseC-Jun N-terminal kinasePhosphatase SHP-1Phosphatidylinositol-3 kinaseMarrow macrophagesAssociation of TRAF6Signal-regulated kinaseN-terminal kinaseMultinuclear osteoclast-like cellsPhosphorylation of AktP85 subunitPhosphatase 1Tyrosine phosphorylationPathways downstreamRANKL-induced phosphorylationRAW264.7 cellsKinasePax5 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
2002
Ly-6 Superfamily Members Ly-6A/E, Ly-6C, and Ly-6I Recognize Two Potential Ligands Expressed by B Lymphocytes
Pflugh DL, Maher SE, Bothwell AL. Ly-6 Superfamily Members Ly-6A/E, Ly-6C, and Ly-6I Recognize Two Potential Ligands Expressed by B Lymphocytes. The Journal Of Immunology 2002, 169: 5130-5136. PMID: 12391229, DOI: 10.4049/jimmunol.169.9.5130.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, B-LymphocyteAntigens, LyB-Lymphocyte SubsetsCD59 AntigensCell Adhesion MoleculesCHO CellsCOS CellsCricetinaeGenetic VariationImmunoglobulin Constant RegionsImmunoglobulin mu-ChainsLectinsLigandsMembrane ProteinsMiceMice, Inbred C57BLMultigene FamilyMyeloid CellsProtein BindingRecombinant Fusion ProteinsSialic Acid Binding Ig-like Lectin 2TransfectionTumor Cells, CulturedConceptsLy-6 proteinsLy-6A/EChimeric proteinLy-6 moleculesMost hemopoietic cellsGlycosylphosphatidylinositol-linked proteinsMature B cellsMembrane proteinsLipid raftsLy-6ECell adhesion moleculeStages of differentiationMature B lymphocytesAnalysis of variantsIgM heavy chainSupergene familyCH27 cellsProteinHemopoietic cellsLigand activityLy-6CHeavy chainPotential ligandsB lymphocytesAdhesion molecules