2025
Enhanced paracrine action of FGF21 in stromal cells delays thymic aging
Youm Y, Gliniak C, Zhang Y, Dlugos T, Scherer P, Dixit V. Enhanced paracrine action of FGF21 in stromal cells delays thymic aging. Nature Aging 2025, 5: 576-587. PMID: 39972172, PMCID: PMC12003152, DOI: 10.1038/s43587-025-00813-5.Peer-Reviewed Original ResearchThymic epithelial cellsThymic agingNaive CD8 T cellsCD8 T cellsAge-related thymic involutionT cell diversityThymic functionImmune dysfunctionThymic stromaT cellsThymic lymphopoiesisThymic involutionActions of FGF21Immune agingAged miceStromal cellsEpithelial cellsAged animalsCo-receptorHepatic overexpressionElevation of FGF21FGF21AgeCellsAdipocytes
2024
Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis-associated thymoma
Yasumizu Y, Kinoshita M, Zhang M, Motooka D, Suzuki K, Nojima S, Koizumi N, Okuzaki D, Funaki S, Shintani Y, Ohkura N, Morii E, Okuno T, Mochizuki H. Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis-associated thymoma. Cell Reports 2024, 43: 114677. PMID: 39180749, DOI: 10.1016/j.celrep.2024.114677.Peer-Reviewed Original ResearchMyasthenia gravisMedullary thymic epithelial cellsGerminal center responseRegulatory T cellsImmune cell compositionMigratory dendritic cellsThymic epithelial cellsCortico-medullary junctionImmune microenvironmentDendritic cellsT cellsChemokine patternsThymus abnormalitiesHyperplasia samplesThymomaSpatial transcriptomic analysisEpithelial cellsMG pathologyMedullary regionCenter responseMedullaCell compositionCortical regionsPathologyCellsA humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses
Chupp D, Rivera C, Zhou Y, Xu Y, Ramsey P, Xu Z, Zan H, Casali P. A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses. Nature Immunology 2024, 25: 1489-1506. PMID: 38918608, PMCID: PMC11291283, DOI: 10.1038/s41590-024-01880-3.Peer-Reviewed Original ResearchConceptsB cellsImmune cell differentiationAntibody responseHumanized micePfizer-BioNTech coronavirus disease 2019T cell antigen receptor repertoireFollicular helper T cellsGerminal center B cellsHuman cord blood CD34Human thymic epithelial cellsT cell-independent antibody responsesImmune systemMarginal zone B cellsMaturation of antibody responsesMemory B cell differentiationCD34+ cellsCord blood CD34Helper T cellsT cell-dependentThymic epithelial cellsNeutralizing antibody responsesB cell differentiationHuman B cellsAntigen receptor repertoireCell differentiation
2022
Myasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma
Yasumizu Y, Ohkura N, Murata H, Kinoshita M, Funaki S, Nojima S, Kido K, Kohara M, Motooka D, Okuzaki D, Suganami S, Takeuchi E, Nakamura Y, Takeshima Y, Arai M, Tada S, Okumura M, Morii E, Shintani Y, Sakaguchi S, Okuno T, Mochizuki H. Myasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma. Nature Communications 2022, 13: 4230. PMID: 35869073, PMCID: PMC9305039, DOI: 10.1038/s41467-022-31951-8.Peer-Reviewed Original ResearchConceptsMedullary thymic epithelial cellsEctopic expressionCellular composition estimationSingle-cell RNA sequencingThymic epithelial cellsSubpopulation of medullary thymic epithelial cellsEpithelial cellsMG-thymomaRNA sequencingGene expressionCell-cell interaction analysisCell migrationComprehensive atlasEctopic germinal center formationInteraction analysisDendritic cell migrationGerminal center formationMyasthenia gravisCellsTranscriptomeCXCL12-CXCR4Cell accumulationT/B cells
2018
Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration
Wertheimer T, Velardi E, Tsai J, Cooper K, Xiao S, Kloss CC, Ottmüller KJ, Mokhtari Z, Brede C, deRoos P, Kinsella S, Palikuqi B, Ginsberg M, Young LF, Kreines F, Lieberman SR, Lazrak A, Guo P, Malard F, Smith OM, Shono Y, Jenq RR, Hanash AM, Nolan DJ, Butler JM, Beilhack A, Manley NR, Rafii S, Dudakov JA, van den Brink MRM. Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration. Science Immunology 2018, 3 PMID: 29330161, PMCID: PMC5795617, DOI: 10.1126/sciimmunol.aal2736.Peer-Reviewed Original ResearchConceptsKey transcription factorEndothelial cellsEndogenous tissue regenerationThymic epithelial cellsTranscription factorsBMP4 pathwayThymic endothelial cellsDownstream targetsBMP4Genetic inhibitionThymocyte developmentTEC developmentEpithelial cellsKey mediatorEndogenous regenerationRemarkable abilityCritical pathwaysTissue regenerationPathwayCellsRegenerationEndogenous thymic regenerationT cell immunityPotential clinical approachThymic damage
2017
Prdm1 Regulates Thymic Epithelial Function To Prevent Autoimmunity
Roberts NA, Adams BD, McCarthy NI, Tooze RM, Parnell SM, Anderson G, Kaech SM, Horsley V. Prdm1 Regulates Thymic Epithelial Function To Prevent Autoimmunity. The Journal Of Immunology 2017, 199: 1250-1260. PMID: 28701508, PMCID: PMC5544928, DOI: 10.4049/jimmunol.1600941.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, AntinuclearAutoantibodiesAutoimmunityEpithelial CellsForkhead Transcription FactorsGene Expression RegulationKeratin-14Lymphocyte ActivationMiceMice, Inbred C57BLMice, NudePositive Regulatory Domain I-Binding Factor 1Thymus GlandT-LymphocytesT-Lymphocytes, RegulatoryTranscription FactorsConceptsThymic epithelial cellsThymic epithelial functionT cellsSelf-reactive T cellsEpithelial functionRegulatory T cell developmentDevelopment of Foxp3Tissue-specific AgsMouse thymic epithelial cellsRegulatory T cellsMedullary thymic epithelial cellsAnti-nuclear AbsCell type-specific deletionT cell developmentDendritic cellsAutoantibody productionAutoimmune diseasesAutoimmune pathologyNude miceAutoimmunityTEC functionConditional deletionCrucial transcription factorMiceEpithelial cells
2016
Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution
Youm YH, Horvath TL, Mangelsdorf DJ, Kliewer SA, Dixit VD. Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 1026-1031. PMID: 26755598, PMCID: PMC4743827, DOI: 10.1073/pnas.1514511113.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantationAge-related thymic involutionCaloric restrictionFGF21 functionThymic involutionThymic agingHormone fibroblast growth factor 21Peripheral T-cell diversityThymic T-cell exportFibroblast growth factor 21Diverse T cell repertoireCortical thymic epithelial cellsLow immune competenceT cell frequenciesStem cell transplantationGrowth factor 21Naïve T cellsMiddle-aged miceT cell repertoireT cell diversityThymic stromal cellsT cell exportThymic epithelial cellsBrown adipose tissueEarly thymocyte progenitors
1999
Cloning of a Novel MHC-Encoded Serine Peptidase Highly Expressed by Cortical Epithelial Cells of the Thymus
Bowlus C, Ahn J, Chu T, Gruen J. Cloning of a Novel MHC-Encoded Serine Peptidase Highly Expressed by Cortical Epithelial Cells of the Thymus. Cellular Immunology 1999, 196: 80-86. PMID: 10527559, DOI: 10.1006/cimm.1999.1543.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigen PresentationAntigens, Differentiation, B-LymphocyteBase SequenceCarboxypeptidasesConsensus SequenceCosmidsEpithelial CellsFluorescent Antibody Technique, IndirectGenesHistocompatibility Antigens Class IIHumansIn Situ HybridizationLysosomesMajor Histocompatibility ComplexMiceMice, Inbred C57BLMolecular Sequence DataSequence AlignmentSequence Homology, Amino AcidSerine EndopeptidasesThymus GlandConceptsCortical thymic epithelial cellsAntigen-presenting cellsThymic epithelial cellsEpithelial cellsMHC class II presentationClass II antigen processingMHC class II antigen processingClass II presentationCortical epithelial cellsMajor histocompatibility complex regionThymic capsuleThymic cortexAntigen presentationT cellsSerine proteasesStrong stainingNovel MHCAntigen processingInvariant chainCathepsin SProteolytic milieuThymusPresentationSitu hybridizationStaining
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