2023
Identification of unstable regulatory and autoreactive effector T cells that are expanded in patients with FOXP3 mutations
Borna Š, Lee E, Nideffer J, Ramachandran A, Wang B, Baker J, Mavers M, Lakshmanan U, Narula M, Garrett A, Schulze J, Olek S, Marois L, Gernez Y, Bhatia M, Chong H, Walter J, Kitcharoensakkul M, Lang A, Cooper M, Bertaina A, Roncarolo M, Meffre E, Bacchetta R. Identification of unstable regulatory and autoreactive effector T cells that are expanded in patients with FOXP3 mutations. Science Translational Medicine 2023, 15: eadg6822. PMID: 38117899, PMCID: PMC11070150, DOI: 10.1126/scitranslmed.adg6822.Peer-Reviewed Original ResearchConceptsAutoreactive effector T cellsEffector T cellsAutoreactive T cellsT cellsThymic-derived regulatory T cellsHematopoietic stem cell transplantationT cell receptor repertoireEctodermal dystrophy syndromeT-cell abnormalitiesRegulatory T cellsStem cell transplantationT cell autoreactivityCell receptor repertoireTranscription factor Foxp3FOXP3 mutationsImmunomodulatory treatmentImmune dysregulationPeripheral toleranceCell transplantationFoxp3 deficiencyTCR sequencingFactor Foxp3Patient's TCell abnormalitiesPatients
2022
Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells
van der Veeken J, Campbell C, Pritykin Y, Schizas M, Verter J, Hu W, Wang Z, Matheis F, Mucida D, Charbonnier L, Chatila T, Rudensky A. Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells. Immunity 2022, 55: 1173-1184.e7. PMID: 35700740, PMCID: PMC9885886, DOI: 10.1016/j.immuni.2022.05.010.Peer-Reviewed Original ResearchConceptsPTreg cellsTranscription factor Foxp3Treg cellsFactor Foxp3Absence of Foxp3Foxp3-independent mannerPeripheral Treg cellsRegulatory T cellsRole of Foxp3Genetic tracingSuppress autoimmunityTolerogenic signalsEffector TT cellsFoxp3Mature CD4Commensal microbiotaCell lineagesCellsCell expansionCell programTTregsColitisCD4Autoimmunity
2021
MTHFD2 is a metabolic checkpoint controlling effector and regulatory T cell fate and function
Sugiura A, Andrejeva G, Voss K, Heintzman D, Xu X, Madden M, Ye X, Beier K, Chowdhury N, Wolf M, Young A, Greenwood D, Sewell A, Shahi S, Freedman S, Cameron A, Foerch P, Bourne T, Garcia-Canaveras J, Karijolich J, Newcomb D, Mangalam A, Rabinowitz J, Rathmell J. MTHFD2 is a metabolic checkpoint controlling effector and regulatory T cell fate and function. Immunity 2021, 55: 65-81.e9. PMID: 34767747, PMCID: PMC8755618, DOI: 10.1016/j.immuni.2021.10.011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCytokinesDisease Models, AnimalDNA MethylationHumansInflammationInflammation MediatorsLymphocyte ActivationMechanistic Target of Rapamycin Complex 1Methylenetetrahydrofolate Dehydrogenase (NADP)MiceMice, TransgenicMutationPurinesSignal TransductionT-Lymphocytes, RegulatoryTh17 CellsConceptsRegulatory T cell differentiationPathogenic T helperInflammatory cytokine productionInflammatory disease modelsTranscription factor Foxp3Potential therapeutic targetT cell differentiationCell metabolic reprogrammingMethylenetetrahydrofolate dehydrogenase 2Metabolic checkpointT helperCytokine productionSuppressive capacityAntigenic stimulationFactor Foxp3Therapeutic targetDisease severityAberrant upregulationDisease modelsRegulatory T cells function in established systemic inflammation and reverse fatal autoimmunity
Hu W, Wang Z, Feng Y, Schizas M, Hoyos B, van der Veeken J, Verter J, Bou-Puerto R, Rudensky A. Regulatory T cells function in established systemic inflammation and reverse fatal autoimmunity. Nature Immunology 2021, 22: 1163-1174. PMID: 34426690, PMCID: PMC9341271, DOI: 10.1038/s41590-021-01001-4.Peer-Reviewed Original ResearchConceptsRegulatory T cellsTreg cellsFatal autoimmune diseaseSystemic inflammationAutoimmune diseasesT cellsPro-inflammatory effector cellsFatal autoimmune inflammationFOXP3 protein expressionSevere tissue inflammationTranscription factor Foxp3Autoimmune inflammationFatal autoimmunityInflammatory mediatorsEffector cellsImmune activationImmunosuppressive functionTissue inflammationDiseased miceImmune homeostasisInflammatory responseFactor Foxp3Long-term protectionInflammationLoss of functionExpression of Foxp3 by T follicular helper cells in end-stage germinal centers
Jacobsen J, Hu W, R Castro T, Solem S, Galante A, Lin Z, Allon S, Mesin L, Bilate A, Schiepers A, Shalek A, Rudensky A, Victora G. Expression of Foxp3 by T follicular helper cells in end-stage germinal centers. Science 2021, 373 PMID: 34437125, PMCID: PMC9007630, DOI: 10.1126/science.abe5146.Peer-Reviewed Original ResearchConceptsFollicular helper cellsGerminal centersHelper cellsFormation of GCsExpression of Foxp3Effective antibody responseTranscription factor Foxp3Acute surgeAntibody responseFactor Foxp3T cellsFoxp3Immunoglobulin somatic hypermutationGC sizeAffinity maturationPotential regulatorCellsEctopic expressionSomatic hypermutationExpressionAntibodies
2015
Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells
Sefik E, Geva-Zatorsky N, Oh S, Konnikova L, Zemmour D, McGuire AM, Burzyn D, Ortiz-Lopez A, Lobera M, Yang J, Ghosh S, Earl A, Snapper SB, Jupp R, Kasper D, Mathis D, Benoist C. Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells. Science 2015, 349: 993-997. PMID: 26272906, PMCID: PMC4700932, DOI: 10.1126/science.aaa9420.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacteriaBacteroidetesColitis, UlcerativeColonForkhead Transcription FactorsHomeostasisHumansImmunity, MucosalIntestinal MucosaMice, Inbred C57BLMicrobiotaNuclear Receptor Subfamily 1, Group F, Member 3SymbiosisT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryTh17 CellsTranscription, GeneticTranscriptomeConceptsRegulatory T cellsImmuno-inflammatory responseT helper 17 (Th17) cell differentiationTranscription factor Foxp3Important effector moleculeRegulatory cellsHuman gut microbiotaFactor Foxp3T cellsRelated cell typesGut microbiotaMouse colonRORγSymbiotic membersIntestinal symbiontsFoxp3Tissue homeostasisEffector moleculesCell differentiationCell typesDistinct populationsCellsDifferent outcomesInflammationPTENtiating autoimmunity through Treg cell deregulation
Ray JP, Craft J. PTENtiating autoimmunity through Treg cell deregulation. Nature Immunology 2015, 16: 139-140. PMID: 25594458, PMCID: PMC4447107, DOI: 10.1038/ni.3082.Peer-Reviewed Original Research
2011
An Innate Role for IL-17
Dominguez-Villar M, Hafler DA. An Innate Role for IL-17. Science 2011, 332: 47-48. PMID: 21454778, DOI: 10.1126/science.1205311.Peer-Reviewed Original ResearchConceptsImmune responseImmune dysregulation polyendocrinopathyAbnormal immune responseRegulatory immune cellsRegulatory T cellsHuman autoimmune disordersCytokine interleukin-17Normal immune responseTranscription factor Foxp3IL-17Interleukin-17Autoimmune disordersAutoimmune diseasesImmune cellsImmune system processFOXP3 geneFactor Foxp3T cellsImmune systemFungal infectionsGenetic mutationsHuman genetic mutationsCytokinesInfectionCell types
2009
The role of the CD58 locus in multiple sclerosis
De Jager PL, Baecher-Allan C, Maier LM, Arthur AT, Ottoboni L, Barcellos L, McCauley JL, Sawcer S, Goris A, Saarela J, Yelensky R, Price A, Leppa V, Patterson N, de Bakker PI, Tran D, Aubin C, Pobywajlo S, Rossin E, Hu X, Ashley CW, Choy E, Rioux JD, Pericak-Vance MA, Ivinson A, Booth DR, Stewart GJ, Palotie A, Peltonen L, Dubois B, Haines JL, Weiner HL, Compston A, Hauser SL, Daly MJ, Reich D, Oksenberg JR, Hafler DA. The role of the CD58 locus in multiple sclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 5264-5269. PMID: 19237575, PMCID: PMC2664005, DOI: 10.1073/pnas.0813310106.Peer-Reviewed Original ResearchConceptsMultiple sclerosisMS subjectsMononuclear cellsCD58 expressionProtective effectMRNA expressionPeripheral blood mononuclear cellsRegulatory T cellsBlood mononuclear cellsTranscription factor Foxp3Dose-dependent increaseCentral nervous systemLymphoblastic cell linesClinical remissionAxonal lossControl subjectsInflammatory diseasesFactor Foxp3T cellsWhole-genome association scansLFA-3Nervous systemProtective allelesPotential mechanismsSclerosis
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