2024
Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8+ T cell adoptive therapies in pre-clinical studies
Wu M, Valenca-Pereira F, Cendali F, Giddings E, Pham-Danis C, Yarnell M, Novak A, Brunetti T, Thompson S, Henao-Mejia J, Flavell R, D’Alessandro A, Kohler M, Rincon M. Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8+ T cell adoptive therapies in pre-clinical studies. Nature Communications 2024, 15: 4444. PMID: 38789421, PMCID: PMC11126743, DOI: 10.1038/s41467-024-48653-y.Peer-Reviewed Original ResearchConceptsMethylation-controlled J proteinCAR-T cellsEfficacy of adoptive T cell therapyCD8+ CAR T cellsAdoptive T cell therapyT-cell therapyCD8 cellsT cellsOvalbumin (OVA)-specific CD8T cell adoptive therapyCD8+ T cellsMelanoma tumors in vivoFunction of T cellsAdoptive cellular therapyMurine B-cell leukemiaPromote T cell functionB-cell leukemiaT cell functionTumors in vivoPre-clinical studiesAnti-tumor activityIn vivo efficacyAdoptive therapyPotential therapeutic strategyEndogenous negative regulator
2023
Cutting Edge: IL-21 and Tissue-Specific Signals Instruct Tbet+CD11c+ B Cell Development following Viral Infection.
Song W, Sanchez G, Mayer D, Blackburn H, Chernova I, Flavell R, Weinstein J, Craft J. Cutting Edge: IL-21 and Tissue-Specific Signals Instruct Tbet+CD11c+ B Cell Development following Viral Infection. The Journal Of Immunology 2023, 210: 1861-1865. PMID: 37133336, PMCID: PMC10247523, DOI: 10.4049/jimmunol.2300027.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationInterleukinsLymphocytic ChoriomeningitisMiceMice, Inbred C57BLMice, KnockoutConceptsAge-associated B cellsIL-21Acute lymphocytic choriomeningitis virus infectionB cellsLymphocytic choriomeningitis virus infectionB cell activationHumoral immunityLymphoid organsVirus infectionMouse modelViral infectionB cell developmentCell activationLymphotoxin αVivo generationTissue-specific signalsInfectionDe novo generationOrgan contributionIFNTissue microenvironmentCell developmentLiverPivotal contributorStage-specific roles
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 signalingEncephalomyelitisCellsExpressionIL17
2020
Evidence for a pathogenic role of extrafollicular, IL-10–producing CCR6+B helper T cells in systemic lupus erythematosus
Facciotti F, Larghi P, Bosotti R, Vasco C, Gagliani N, Cordiglieri C, Mazzara S, Ranzani V, Rottoli E, Curti S, Penatti A, Karnani B, Kobayashi Y, Crosti M, Bombaci M, van Hamburg JP, Rossetti G, Gualtierotti R, Gerosa M, Gatti S, Torretta S, Pignataro L, Tas SW, Abrignani S, Pagani M, Grassi F, Meroni PL, Flavell RA, Geginat J. Evidence for a pathogenic role of extrafollicular, IL-10–producing CCR6+B helper T cells in systemic lupus erythematosus. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 7305-7316. PMID: 32184325, PMCID: PMC7132288, DOI: 10.1073/pnas.1917834117.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusHelper T cellsT cellsIL-10Pathogenic roleSLE patientsLupus erythematosusIL-7RB cellsPathogenic anti-dsDNA antibodiesFollicular helper T cellsAnti-dsDNA antibodiesLupus-like diseaseT cell populationsB cell responsesProduction ex vivoCytokine reporter miceProminent pathogenic roleImmunoglobulin G productionNaïve B cellsIL-17Antiinflammatory cytokinesLymph nodesInterleukin-10Peripheral blood
2014
Immunoglobulin A Coating Identifies Colitogenic Bacteria in Inflammatory Bowel Disease
Palm NW, de Zoete MR, Cullen TW, Barry NA, Stefanowski J, Hao L, Degnan PH, Hu J, Peter I, Zhang W, Ruggiero E, Cho JH, Goodman AL, Flavell RA. Immunoglobulin A Coating Identifies Colitogenic Bacteria in Inflammatory Bowel Disease. Cell 2014, 158: 1000-1010. PMID: 25171403, PMCID: PMC4174347, DOI: 10.1016/j.cell.2014.08.006.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseBowel diseaseIgA coatingIntestinal microbiotaIntestinal bacteriaGerm-free miceIBD patientsIntestinal diseaseImmunoglobulin AMouse modelDiseaseAnaerobic culturingDramatic susceptibilityTargeted eliminationDisease developmentDisease susceptibilityMiceCell sortingMicrobiotaBacterial cell sortingFecal bacteriaSuch bacteriaColitisPatientsIgA
2011
NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis
Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA, Booth CJ, Peaper DR, Bertin J, Eisenbarth SC, Gordon JI, Flavell RA. NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis. Cell 2011, 145: 745-757. PMID: 21565393, PMCID: PMC3140910, DOI: 10.1016/j.cell.2011.04.022.Peer-Reviewed Original ResearchConceptsDextran sodium sulfateDamage-associated molecular patternsIL-18 levelsInflammatory cell recruitmentInflammasome-deficient miceWild-type miceColonic microbial ecologyMouse colonic epithelial cellsColonic epithelial cellsColitogenic activityDSS colitisHuman IBDChemical colitisIL-18Antibiotic treatmentInflammasome pathwayNLRP6 inflammasomeCell recruitmentIntestinal hyperplasiaColitisCaspase-1Fecal microbiotaMolecular patternsEpithelial cellsExacerbation
1994
Thymic development in human CD4 transgenic mice. Positive selection occurs after commitment to the CD8 lineage.
Paterson RK, Burkly LC, Kurahara DK, Dunlap A, Flavell RA, Finkel TH. Thymic development in human CD4 transgenic mice. Positive selection occurs after commitment to the CD8 lineage. The Journal Of Immunology 1994, 153: 3491-503. PMID: 7930572, DOI: 10.4049/jimmunol.153.8.3491.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4 AntigensCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHumansMaleMiceMice, Inbred C57BLMice, TransgenicReceptors, Antigen, T-CellSelection, GeneticStochastic ProcessesThymus GlandT-Lymphocyte Subsets