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 rejectionIntranuclear delivery of the transcription modulation domain of Tbet-improved lupus nephritis in (NZB/NZW) F1 lupus-prone mice
Moon JS, Mun CH, Kim JH, Cho JY, Park SD, Park TY, Shin JS, Ho CC, Park YB, Ghosh S, Bothwell ALM, Lee SW, Lee SK. Intranuclear delivery of the transcription modulation domain of Tbet-improved lupus nephritis in (NZB/NZW) F1 lupus-prone mice. Kidney International 2018, 93: 1118-1130. PMID: 29409726, DOI: 10.1016/j.kint.2017.11.017.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsAnti-Inflammatory AgentsCell NucleusCellular MicroenvironmentCytokinesDisease Models, AnimalFemaleInflammation MediatorsKidneyLupus NephritisMice, Inbred NZBProtein DomainsRecombinant ProteinsSpleenT-Box Domain ProteinsT-Lymphocytes, Helper-InducerT-Lymphocytes, RegulatoryTranscription, GeneticConceptsLupus-prone miceTranscription modulation domainSystemic lupus erythematosusCell subsetsTh1-mediated autoimmune diseasesNucleus-transducible formNumber of Th1Severity of nephritisT cell subsetsT cell activationProinflammatory microenvironmentTh17 cellsTreg cellsImmunosuppressive cytokinesLupus patientsLupus erythematosusAutoimmune diseasesImmune therapeuticsF1 miceCell activationExcessive expressionMiceTbetMarked increaseMethylprednisolone
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
2014
PPARγ Negatively Regulates T Cell Activation to Prevent Follicular Helper T Cells and Germinal Center Formation
Park HJ, Kim DH, Choi JY, Kim WJ, Kim JY, Senejani AG, Hwang SS, Kim LK, Tobiasova Z, Lee GR, Craft J, Bothwell AL, Choi JM. PPARγ Negatively Regulates T Cell Activation to Prevent Follicular Helper T Cells and Germinal Center Formation. PLOS ONE 2014, 9: e99127. PMID: 24921943, PMCID: PMC4055678, DOI: 10.1371/journal.pone.0099127.Peer-Reviewed Original ResearchConceptsFollicular helper T cellsHelper T cellsT cellsGerminal center reactionTfh cellsSheep red blood cell immunizationRed blood cell immunizationCenter reactionPeroxisome proliferator-activated receptor gammaIL-21 expressionProliferator-activated receptor gammaWild-type T cellsType T cellsGerminal center formationGerminal center B cellsT cell activationCell immunizationAutoantibody productionGlomerular inflammationSignature cytokinesAdaptive immunityGerminal centersGlucose metabolismNF-κBB cells
2012
The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases
Choi JM, Bothwell AL. The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases. Molecules And Cells 2012, 33: 217-222. PMID: 22382683, PMCID: PMC3887706, DOI: 10.1007/s10059-012-2297-y.Peer-Reviewed Original ResearchConceptsPeroxisome proliferator-activated receptorIndependent regulatory mechanismsImportant regulatory roleNuclear receptor proteinsT helper cell differentiationTranscription factorsCellular differentiationNuclear receptor peroxisome proliferator-activated receptorGene expressionRegulatory mechanismsDiverse rolesHelper cell differentiationT cell survivalPPARβ/δCell differentiationRegulatory roleImportant regulatorReceptor proteinNuclear receptorsT cell activationProliferator-activated receptorAutoimmune diseasesLigand treatmentProteinSynthetic ligands
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 potential
2008
Transduction of the cytoplasmic domain of CTLA-4 inhibits TcR-specific activation signals and prevents collagen-induced arthritis
Choi JM, Kim SH, Shin JH, Gibson T, Yoon BS, Lee DH, Lee SK, Bothwell AL, Lim JS, Lee SK. Transduction of the cytoplasmic domain of CTLA-4 inhibits TcR-specific activation signals and prevents collagen-induced arthritis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 19875-19880. PMID: 19066215, PMCID: PMC2604944, DOI: 10.1073/pnas.0805198105.Peer-Reviewed Original ResearchConceptsCollagen-induced arthritisT cell activationCTLA-4Human umbilical vein endothelial cellsCell activationInflammatory cytokine productionErosion of cartilageCytoplasmic domainEffective therapeutic approachActivated T cellsUmbilical vein endothelial cellsCell-permeable formT cell receptor-proximal signalingVein endothelial cellsAntibody levelsRheumatoid arthritisAutoimmune diseasesCytokine productionHuman CTLT cellsTherapeutic approachesCell-permeable recombinant proteinArthritisTransdermal administrationMouse T cell activation
2004
Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor ζ chain ITAMs and their tyrosine residues
Chae WJ, Lee HK, Han JH, Kim SW, Bothwell AL, Morio T, Lee SK. Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor ζ chain ITAMs and their tyrosine residues. International Immunology 2004, 16: 1225-1236. PMID: 15302845, DOI: 10.1093/intimm/dxh120.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseTCR zeta chainTyrosine phosphorylated proteinsTyrosine residuesZeta chainPhosphorylated proteinsT cell activationCell deathFirst tyrosine residueCell activationInfluence of mutationsActivation-induced cell deathProtein kinaseDistinctive regulationIntracellular signalsDifferential regulationITAMMAPK phosphorylationTCR stimulationStepwise deletionJurkat transfectantsDistinct signalsActivation signalsMutationsResidues