2024
Mechanism of Hyperactive PLCγ1 Signaling in T-Cell Leukemia/Lymphoma
Zeng L, Zhang X, Xiong Y, Hajicek N, Sondek J, Su X. Mechanism of Hyperactive PLCγ1 Signaling in T-Cell Leukemia/Lymphoma. Blood 2024, 144: 48-48. DOI: 10.1182/blood-2024-193065.Peer-Reviewed Original ResearchHDACi resistancePeripheral T-cell lymphomaCutaneous T-cell lymphomaAdult T-cell leukemia/lymphomaLiquid-liquid phase separationT-cell lymphomaT-cell leukemia/lymphomaT cell proliferationHistone deacetylasesTotal internal reflection fluorescenceT cellsTCR signalingDrug resistanceDysregulation of LLPSWild typeMolecular mechanismsAberrant protein aggregationInhibitor resistanceResistance to HDAC inhibitorsMemory T cell developmentT cell receptor signalingActivation of T cellsPromote T cell proliferationT-cell malignanciesBcl-2 expressionPD-1 defines a distinct, functional, tissue-adapted state in Vδ1+ T cells with implications for cancer immunotherapy
Davies D, Kamdar S, Woolf R, Zlatareva I, Iannitto M, Morton C, Haque Y, Martin H, Biswas D, Ndagire S, Munonyara M, Gillett C, O’Neill O, Nussbaumer O, Hayday A, Wu Y. PD-1 defines a distinct, functional, tissue-adapted state in Vδ1+ T cells with implications for cancer immunotherapy. Nature Cancer 2024, 5: 420-432. PMID: 38172341, PMCID: PMC10965442, DOI: 10.1038/s43018-023-00690-0.Peer-Reviewed Original ResearchConceptsCheckpoint inhibitionPD-1T cellsProgrammed cell death protein 1Cell death protein 1PD-1 expressionResponse to TCR signalingPD-1 engagementT cell recognitionCancer immunotherapyTCR signalingTranscriptomic programsProtein 1CancerFunctional relevanceCellsImmunotherapyNeoantigensMelanomaPatientsOncology
2022
Cholinergic control of Th17 cell pathogenicity in experimental autoimmune encephalomyelitis
Nechanitzky R, Nechanitzky D, Ramachandran P, Duncan G, Zheng C, Göbl C, Gill K, Haight J, Wakeham A, Snow B, Bradaschia-Correa V, Ganguly M, Lu Z, Saunders M, Flavell R, Mak T. Cholinergic control of Th17 cell pathogenicity in experimental autoimmune encephalomyelitis. Cell Death & Differentiation 2022, 30: 407-416. PMID: 36528755, PMCID: PMC9950465, DOI: 10.1038/s41418-022-01092-y.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisTh17 cellsMultiple sclerosisAutoimmune encephalomyelitisChAT expressionBrain-infiltrating immune cellsStrong TCR signalingCholinergic controlTherapeutic immunomodulationCholine acetyltransferaseImmune cellsCell pathogenicityDisease progressionChronic activationMouse modelTranscription factor Bhlhe40Novel targetAcetylcholineMRNA levelsPathogenic determinantsTCR signalingEncephalomyelitisCellsExpressionIL17SILAC Phosphoproteomics Reveals Unique Signaling Circuits in CAR‑T Cells and the Inhibition of B Cell-Activating Phosphorylation in Target Cells
Griffith AA, Callahan KP, King NG, Xiao Q, Su X, Salomon AR. SILAC Phosphoproteomics Reveals Unique Signaling Circuits in CAR‑T Cells and the Inhibition of B Cell-Activating Phosphorylation in Target Cells. Journal Of Proteome Research 2022, 21: 395-409. PMID: 35014847, PMCID: PMC8830406, DOI: 10.1021/acs.jproteome.1c00735.Peer-Reviewed Original ResearchConceptsCD19 CAR T cellsChimeric antigen receptorRaji B cellsT cellsB cellsCAR T cell activityT cell activityB-cell malignanciesT cell receptor signalingCAR T cell signalingCell receptor signalingCD19-CARCell malignanciesT cell signalingCell activityReceptor signalingAntigen receptorLiquid chromatography-tandem mass spectrometryTarget cellsSignificant decreaseChromatography-tandem mass spectrometryTCR signalingReceptorsResponse of cellsCells
2020
Rewired signaling network in T cells expressing the chimeric antigen receptor (CAR)
Dong R, Libby KA, Blaeschke F, Fuchs W, Marson A, Vale RD, Su X. Rewired signaling network in T cells expressing the chimeric antigen receptor (CAR). The EMBO Journal 2020, 39: embj2020104730. PMID: 32643825, PMCID: PMC7429742, DOI: 10.15252/embj.2020104730.Peer-Reviewed Original ResearchConceptsCentral supramolecular activation clusterEssential scaffold proteinT cell receptorSupramolecular activation clusterImmunological synapse formationAntigen receptorActin remodelingScaffold proteinMicrocluster formationDownstream signalingTCR signalingT cell activationSynapse formationCancer cellsSpecific cancer cellsCell receptorSignalingCAR activationT cellsCell activationCellsCAR-T cell activationNative T cellsPathwayActivation clusters
2019
Reporters of TCR signaling identify arthritogenic T cells in murine and human autoimmune arthritis
Ashouri JF, Hsu LY, Yu S, Rychkov D, Chen Y, Cheng DA, Sirota M, Hansen E, Lattanza L, Zikherman J, Weiss A. Reporters of TCR signaling identify arthritogenic T cells in murine and human autoimmune arthritis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 18517-18527. PMID: 31455730, PMCID: PMC6744919, DOI: 10.1073/pnas.1904271116.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsArthritis, ExperimentalArthritis, RheumatoidBiopsyCD4-Positive T-LymphocytesCell DifferentiationDown-RegulationFemaleGenes, ReporterGreen Fluorescent ProteinsHumansInterleukin-17Interleukin-6MaleMiceMice, TransgenicMiddle AgedNuclear Receptor Subfamily 4, Group A, Member 1Receptors, Antigen, T-CellSignal TransductionSuppressor of Cytokine Signaling 3 ProteinSynovectomySynovial MembraneTh17 CellsZymosanConceptsCD4 T cellsRheumatoid arthritisT cellsSKG miceAutoimmune arthritisDifferentiation 4 (CD4) T cellsReceptor signalingHuman autoimmune arthritisIL-6 receptor signalingSKG mouse modelAutoreactive T cellsArthritogenic T cellsIL-6 cytokinesTCR signalingIL-6 signalingRA synoviumSuppressor of cytokineArthritogenic potentialInterleukin-17IL-6Autoantigen exposureEnhanced autoreactivityMouse modelAntigen receptor signalingNur77-eGFP
2017
Autoimmunity Checkpoints As Therapeutic Targets in B- and T-Cell Malignancies
Chen Z, Hecht A, Muschen M. Autoimmunity Checkpoints As Therapeutic Targets in B- and T-Cell Malignancies. Blood 2017, 130: 718. DOI: 10.1182/blood.v130.suppl_1.718.718.Peer-Reviewed Original ResearchInducible T Cell Kinase Regulates the Acquisition of Cytolytic Capacity and Degranulation in CD8+ CTLs
Kapnick S, Stinchcombe J, Griffiths G, Schwartzberg P. Inducible T Cell Kinase Regulates the Acquisition of Cytolytic Capacity and Degranulation in CD8+ CTLs. The Journal Of Immunology 2017, 198: 2699-2711. PMID: 28213500, PMCID: PMC5360469, DOI: 10.4049/jimmunol.1601202.Peer-Reviewed Original ResearchConceptsInducible T-cell kinaseT-cell kinaseITK deficiencyCD8<sup>+</sup> T cell functionCD8<sup>+</sup> T cellsAcquisition of effector functionsExposure to IL-2CD8<sup>+</sup> CTLsCD8+ CTLT cell functionSusceptibility to viral infectionsCTL expansionCytolytic capacityCytolytic effectorsT cellsIL-12IL-2Effector functionsMurine CTLTCR signalingViral infectionMurine cellsDefective functionCTLCytokine signaling
2016
T Cell Receptor Mediated Calcium Entry Requires Alternatively Spliced Cav1.1 Channels
Matza D, Badou A, Klemic KG, Stein J, Govindarajulu U, Nadler MJ, Kinet JP, Peled A, Shapira OM, Kaczmarek LK, Flavell RA. T Cell Receptor Mediated Calcium Entry Requires Alternatively Spliced Cav1.1 Channels. PLOS ONE 2016, 11: e0147379. PMID: 26815481, PMCID: PMC4729531, DOI: 10.1371/journal.pone.0147379.Peer-Reviewed Original Research
2014
Single-cell mass cytometry of TCR signaling: Amplification of small initial differences results in low ERK activation in NOD mice
Mingueneau M, Krishnaswamy S, Spitzer MH, Bendall SC, Stone EL, Hedrick SM, Pe'er D, Mathis D, Nolan GP, Benoist C. Single-cell mass cytometry of TCR signaling: Amplification of small initial differences results in low ERK activation in NOD mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 16466-16471. PMID: 25362052, PMCID: PMC4246343, DOI: 10.1073/pnas.1419337111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 1Disease Models, AnimalEnzyme ActivationExtracellular Signal-Regulated MAP KinasesGenetic VariationI-kappa B ProteinsImmune ToleranceImmunity, CellularImmunologic Deficiency SyndromesImmunologic MemoryLymph NodesLymphopoiesisMaleMAP Kinase Signaling SystemMass SpectrometryMiceMice, Inbred C57BLMice, Inbred NODMice, KnockoutMitogen-Activated Protein Kinase 1NF-KappaB Inhibitor alphaPhosphorylationProtein Processing, Post-TranslationalReceptors, Antigen, T-CellSelf ToleranceSingle-Cell AnalysisThymus GlandConceptsT cellsT cell differentiationNOD T cellsERK activationNonobese diabetic (NOD) miceMemory T cellsKO T cellsMass cytometrySingle-cell mass cytometryNOD miceDiabetic miceB6 miceControl C57BL/6Small impairmentMicePrimary deficiencyTCR signalingPhosphorylation levelsLarge defectsTCR triggeringActivationLower ERK activationImpairmentCytometryCells
2007
An Association Between the Autoimmune Susceptibility Locus CTLA4 and Alterations in Proximal TCR Signaling in Healthy Human Volunteers
Maier L, Anderson D, de Jager P, Hafler D, Wicker L. An Association Between the Autoimmune Susceptibility Locus CTLA4 and Alterations in Proximal TCR Signaling in Healthy Human Volunteers. Clinical Immunology 2007, 123: s135. DOI: 10.1016/j.clim.2007.03.023.Peer-Reviewed Original Research
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