Featured Publications
Human autoinflammatory disease reveals ELF4 as a transcriptional regulator of inflammation
Tyler PM, Bucklin ML, Zhao M, Maher TJ, Rice AJ, Ji W, Warner N, Pan J, Morotti R, McCarthy P, Griffiths A, van Rossum AMC, Hollink IHIM, Dalm VASH, Catanzaro J, Lakhani SA, Muise AM, Lucas CL. Human autoinflammatory disease reveals ELF4 as a transcriptional regulator of inflammation. Nature Immunology 2021, 22: 1118-1126. PMID: 34326534, PMCID: PMC8985851, DOI: 10.1038/s41590-021-00984-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalgranulin ADNA-Binding ProteinsFemaleGene Expression RegulationHereditary Autoinflammatory DiseasesHumansInflammatory Bowel DiseasesInterleukin 1 Receptor Antagonist ProteinLipocalin-2LipopolysaccharidesMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutTh17 CellsTranscription FactorsTranscription, GeneticTriggering Receptor Expressed on Myeloid Cells-1ConceptsInterleukin-1Inflammatory bowel disease (IBD) characteristicsInflammatory immune cellsHuman inflammatory disordersAnti-inflammatory genesTumor necrosis factorHuman autoinflammatory diseasesInnate stimuliHyperinflammatory responseMale patientsNeutrophil chemoattractantDisease characteristicsInflammatory disordersMucosal diseaseImmune cellsInflammation amplifierNecrosis factorUnrelated male patientsAutoinflammatory diseasesMouse modelBroad translational relevanceTranslational relevanceInflammationFunction variantsMouse macrophagesHuman PI3Kγ deficiency and its microbiota-dependent mouse model reveal immunodeficiency and tissue immunopathology
Takeda AJ, Maher TJ, Zhang Y, Lanahan SM, Bucklin ML, Compton SR, Tyler PM, Comrie WA, Matsuda M, Olivier KN, Pittaluga S, McElwee JJ, Long Priel DA, Kuhns DB, Williams RL, Mustillo PJ, Wymann MP, Koneti Rao V, Lucas CL. Human PI3Kγ deficiency and its microbiota-dependent mouse model reveal immunodeficiency and tissue immunopathology. Nature Communications 2019, 10: 4364. PMID: 31554793, PMCID: PMC6761123, DOI: 10.1038/s41467-019-12311-5.Peer-Reviewed Original ResearchConceptsT cellsAppropriate adaptive immune responsePet store miceRegulatory T cellsCD4 T cellsAnti-inflammatory functionsAdaptive immune responsesLymphocytic pneumonitisPI3Kγ deficiencyTissue immunopathologyIL-23Memory CD8IL-12TLR stimulationImmune modulationImmune responseGSK3α/βMouse modelMemory BHuman patientsMiceDependent mannerP110γ catalytic subunitFunction mutationsDrug targets
2011
LAG-3, TGF-β, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L
Lucas CL, Workman CJ, Beyaz S, LoCascio S, Zhao G, Vignali DA, Sykes M. LAG-3, TGF-β, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L. Blood 2011, 117: 5532-5540. PMID: 21422469, PMCID: PMC3109721, DOI: 10.1182/blood-2010-11-318675.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntigens, CDAntigens, SurfaceApoptosis Regulatory ProteinsB7-1 AntigenB7-H1 AntigenBone Marrow TransplantationCD4-Positive T-LymphocytesCD40 LigandCD8-Positive T-LymphocytesCTLA-4 AntigenFemaleImmune ToleranceLymphocyte Activation Gene 3 ProteinMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicModels, ImmunologicalPeptidesProgrammed Cell Death 1 Ligand 2 ProteinProgrammed Cell Death 1 ReceptorSignal TransductionTransforming Growth Factor betaTransplantation, HomologousConceptsT cell toleranceCD4 T cell tolerancePeripheral CD8PD-1LAG-3T cellsCD8 T cell tolerance inductionPD-1/PD-L1 pathwayCD8 T cell tolerancePD-1 inhibitory pathwayT cell tolerance inductionAdoptive transfer studiesAllogeneic BM transplantationPD-L1 pathwayAlloreactive T cellsMixed hematopoietic chimerismT cell-intrinsic requirementB7.1/B7.2Cell-intrinsic requirementTGF-β signalingAllogeneic BMTPD-L1Mixed chimerasPD-L2Tolerance induction
2009
A CD8 T cell–intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo
Fehr T, Lucas CL, Kurtz J, Onoe T, Zhao G, Hogan T, Vallot C, Rao A, Sykes M. A CD8 T cell–intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo. Blood 2009, 115: 1280-1287. PMID: 20007805, PMCID: PMC2826238, DOI: 10.1182/blood-2009-07-230680.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalApoptosis Regulatory ProteinsBone Marrow TransplantationCalcineurinCD4-Positive T-LymphocytesCD40 LigandCD8-Positive T-LymphocytesCyclosporineFemaleFlow CytometryGraft SurvivalImmune ToleranceMiceMice, Inbred C57BLMice, TransgenicNFATC Transcription FactorsReceptors, Antigen, T-CellSignal TransductionThymectomyTransplantation ChimeraConceptsCD8 T cellsCalcineurin/NFAT pathwayTolerance inductionCD8 toleranceT cell receptorCD4 cellsT cellsAllogeneic bone marrow transplantation modelNFAT pathwayT cell-intrinsic roleAnti-CD154 antibodyFailure of CD8Adoptive transfer studiesBone marrow transplantation modelBone marrow transplantationCell-intrinsic roleCalcineurin-NFAT pathwayCD8 cellsRegulatory cellsTransplantation toleranceMarrow transplantationTransplantation modelAnergy inductionNFAT1 deficiencyNuclear factor
2008
Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway
Haspot F, Fehr T, Gibbons C, Zhao G, Hogan T, Honjo T, Freeman GJ, Sykes M. Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway. Blood 2008, 112: 2149-2155. PMID: 18577709, PMCID: PMC2518911, DOI: 10.1182/blood-2007-12-127449.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen-Presenting CellsAntigens, SurfaceApoptosis Regulatory ProteinsB7-1 AntigenB7-H1 AntigenBone Marrow TransplantationCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleImmune ToleranceLymphocyte ActivationMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicModels, ImmunologicalPeptidesProgrammed Cell Death 1 ReceptorTransplantation, HomologousConceptsPD-1/PD-L1 pathwayPD-L1 pathwayBone marrow transplantationCD4 cellsCD8 cellsAlloreactive CD8PD-1Low-dose total body irradiationAlloreactive T cell populationsAllogeneic bone marrow transplantationAlloreactive CD8 cellsAnti-CD154 antibodyCD8 cell responsesTotal body irradiationCD4 T cellsLigand PD-L1T cell populationsRapid tolerizationCD4 helpDeath-1PD-L1Body irradiationMarrow transplantationActivation markersChronic infection