2025
Broxyquinoline targets NLRP3 to inhibit inflammasome activation and alleviate NLRP3-associated inflammatory diseases
Tang H, Zou X, Chen P, Wang Y, Gao S, Wang T, Xu Y, Ji S. Broxyquinoline targets NLRP3 to inhibit inflammasome activation and alleviate NLRP3-associated inflammatory diseases. International Immunopharmacology 2025, 156: 114687. PMID: 40253767, DOI: 10.1016/j.intimp.2025.114687.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisNLR family pyrin domain-containing 3Inflammasome activationInflammatory diseasesASC speck formationInflammasome-associated diseasesNEK7-NLRP3 interactionDamage signalingNF-kB pathwayHost defensePyrin domain-containing 3Speck formationAIM2 inflammasome activationActivation of NLRP3 inflammasomeFamily pyrin domain-containing 3Autoimmune encephalomyelitisMurine modelInterleukin-1bIL-1BInhibiting inflammasome activationNLRP3 inflammasome inhibitorAntimicrobial drugsNF-kBProteinTherapeutic agents
2024
Neuroprotective effect of neuron‐specific deletion of the C16 ceramide synthetic enzymes in an animal model of multiple sclerosis
Amatruda M, Marechal D, Gacias M, Wentling M, Turpin‐Nolan S, Morstein J, Moniruzzaman M, Brüning J, Haughey N, Trauner D, Casaccia P. Neuroprotective effect of neuron‐specific deletion of the C16 ceramide synthetic enzymes in an animal model of multiple sclerosis. Glia 2024, 73: 271-290. PMID: 39489703, PMCID: PMC11662985, DOI: 10.1002/glia.24631.Peer-Reviewed Original ResearchExperimental autoimmune encephalomyelitisNeuron-specific deletionMultiple sclerosisDemyelinating disordersCourse of EAESalvage pathwayAnimal model of multiple sclerosisModel of multiple sclerosisDisease severityRecycling of sphingosineWild type miceCeramide synthase 6Central nervous systemPalmitic acidAutoimmune encephalomyelitisExposure to oxidative stressType miceInflammatory demyelinationMyelin damageSaturated fatAnimal modelsMitochondrial dysfunctionCerS5Nervous systemNeuroprotective effectsGastrodenol suppresses NLRP3/GSDMD mediated pyroptosis and ameliorates inflammatory diseases
Chen P, Wang Y, Tang H, Liu Z, Wang J, Wang T, Xu Y, Ji S. Gastrodenol suppresses NLRP3/GSDMD mediated pyroptosis and ameliorates inflammatory diseases. Cellular Immunology 2024, 405: 104888. PMID: 39486308, DOI: 10.1016/j.cellimm.2024.104888.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytokinesEncephalomyelitis, Autoimmune, ExperimentalFemaleGasderminsHumansInflammasomesInflammationIntracellular Signaling Peptides and ProteinsLipopolysaccharidesMacrophagesMiceMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinPeritonitisPhosphate-Binding ProteinsPyroptosisConceptsNucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3Caspase activationRecruitment domainNLRP3 oligomerizationPyrin domain-containing protein 3Gasdermin D (GSDMD)-mediated pyroptosisProtein 3PyroptosisSecretion of pro-inflammatory cytokinesOligomerizationHydrogen bondsApoptosis-associated speck like proteinInflammatory diseasesTherapeutic strategiesHelicobacter pyloriPro-inflammatory cytokinesCaspaseExperimental autoimmune encephalomyelitisLipopolysaccharide (LPS)-inducedProteinGasdermin
2023
Cutting Edge: Serpine1 Negatively Regulates Th1 Cell Responses in Experimental Autoimmune Encephalomyelitis.
Akbar I, Tang R, Baillargeon J, Roy A, Doss P, Zhu C, Kuchroo V, Rangachari M. Cutting Edge: Serpine1 Negatively Regulates Th1 Cell Responses in Experimental Autoimmune Encephalomyelitis. The Journal Of Immunology 2023, 211: 1762-1766. PMID: 37909848, DOI: 10.4049/jimmunol.2300526.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisTh1 cellsTim-3Autoimmune encephalomyelitisTh1 cell responsesCell cytokine productionInhibitors of IFNExpression of IFNEAE phenotypeCytokine productionMild diseaseInhibitory receptorsLAG-3T cellsEnhanced severityKnockout miceCell responsesReduced expressionEncephalomyelitisTargeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation
Schnell A, Huang L, Regan B, Singh V, Vonficht D, Bollhagen A, Wang M, Hou Y, Bod L, Sobel R, Chihara N, Madi A, Anderson A, Regev A, Kuchroo V. Targeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation. Nature Immunology 2023, 24: 1908-1920. PMID: 37828379, PMCID: PMC10864036, DOI: 10.1038/s41590-023-01645-4.Peer-Reviewed Original ResearchConceptsPeptidoglycan recognition protein 1T cellsMyeloid cellsGenetic deletionPotent antitumor immune responsesCo-inhibitory moleculesExperimental autoimmune encephalomyelitisAntitumor immune responseImmune checkpoint blockadePromising targetSuccessful treatment optionT cell functionCentral nervous systemT cell activationMultiple human cancersAutoimmune neuroinflammationAntitumor immunityAutoimmune encephalomyelitisCheckpoint blockadeCheckpoint moleculesEffector phenotypeAutoimmune diseasesProinflammatory moleculesTissue inflammationTreatment optionsTMEM106B Puncta Is Increased in Multiple Sclerosis Plaques, and Reduced Protein in Mice Results in Delayed Lipid Clearance Following CNS Injury
Shafit-Zagardo B, Sidoli S, Goldman J, DuBois J, Corboy J, Strittmatter S, Guzik H, Edema U, Arackal A, Botbol Y, Merheb E, Nagra R, Graff S. TMEM106B Puncta Is Increased in Multiple Sclerosis Plaques, and Reduced Protein in Mice Results in Delayed Lipid Clearance Following CNS Injury. Cells 2023, 12: 1734. PMID: 37443768, PMCID: PMC10340176, DOI: 10.3390/cells12131734.Peer-Reviewed Original ResearchConceptsAxonal damageMultiple sclerosisRelapsing-remitting multiple sclerosisHypomorphic miceExperimental autoimmune encephalomyelitisRelapsing-remitting MSNormal-appearing white matterMultiple sclerosis plaquesWhite matter plaquesNon-neurologic controlsWild-type miceBrains of individualsLipid droplet accumulationAutoimmune encephalomyelitisMyelin oligodendrocyteCNS injuryLipid clearanceSpinal cordNeuronal integrityTransmembrane protein 106BWhite matterAlzheimer's diseaseMice resultsDroplet accumulationPlaquesVery-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation
Chung H, Ye Q, Park Y, Zuo Z, Mok J, Kanca O, Tattikota S, Lu S, Perrimon N, Lee H, Bellen H. Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation. Cell Metabolism 2023, 35: 855-874.e5. PMID: 37084732, PMCID: PMC10160010, DOI: 10.1016/j.cmet.2023.03.022.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisMultiple sclerosisAdministration of fingolimodFunctions of S1PNF-κB activationSphingosine-1-phosphate (S1P) synthesisS1P receptor antagonistsElevated VLCFAAutoimmune encephalomyelitisFatty acidsMacrophage infiltrationReceptor antagonistImmune cellsMouse modelTreatment avenuesVLCFA levelsFly gliaLong-chain fatty acidsGliaS1P pathwayS1PNeuroinflammationFingolimodVLCFAAbundant fatty acidsNogo receptor-Fc delivered by haematopoietic cells enhances neurorepair in a multiple sclerosis model
Ye S, Theotokis P, Lee J, Kim M, Nheu D, Ellen O, Bedford T, Ramanujam P, Wright D, McDonald S, Alrehaili A, Bakhuraysah M, Kang J, Siatskas C, Tremblay C, Curtis D, Grigoriadis N, Monif M, Strittmatter S, Petratos S. Nogo receptor-Fc delivered by haematopoietic cells enhances neurorepair in a multiple sclerosis model. Brain Communications 2023, 5: fcad108. PMID: 37091588, PMCID: PMC10116608, DOI: 10.1093/braincomms/fcad108.Peer-Reviewed Original ResearchExperimental autoimmune encephalomyelitisAutoimmune encephalomyelitisHaematopoietic stem cellsFc fusion proteinMultiple sclerosisAnimal modelsExperimental autoimmune encephalomyelitis lesionsCNS-infiltrating macrophagesStem cellsMultiple sclerosis modelInflammatory cell infiltrateNogo receptor 1Spinal cord injuryContext of neuroinflammationRecipient female miceImmune cell lineagesHigh-affinity receptorDisease-specific mannerDifferentiated phagocytesNeurological recoveryExtensive demyelinationAxonal damageCell infiltrateCNS lesionsNeurological decline
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 signalingEncephalomyelitisCellsExpressionIL17Dectin-1 signaling in neutrophils up-regulates PD-L1 and triggers ROS-mediated suppression of CD4+ T cells
Deerhake ME, Cardakli ED, Shinohara ML. Dectin-1 signaling in neutrophils up-regulates PD-L1 and triggers ROS-mediated suppression of CD4+ T cells. Journal Of Leukocyte Biology 2022, 112: 1413-1425. PMID: 36073780, PMCID: PMC9701158, DOI: 10.1002/jlb.3a0322-152rr.Peer-Reviewed Original ResearchConceptsPD-L1 expressionExperimental autoimmune encephalomyelitisPD-L1T cellsT cell-suppressive propertiesUp-regulating PD-L1T cell-driven inflammationImmune checkpoint factorsNeutrophil PD-L1Suppression of CD4T cell responsesProinflammatory cytokine productionT cell viabilityHost defense functionsAutoimmune encephalomyelitisDendritic cellsCytokine productionMHC-IINeutrophil responseCD4Disease severityCell responsesNeutrophilsFungal infectionsReactive oxygen species“Near Cure” treatment of severe acute EAE in MIF-1-deficient female and male mice with a bifunctional MHCII-derived molecular construct
Vandenbark AA, Meza-Romero R, Wiedrick J, Gerstner G, Seifert H, Kent G, Piechycna M, Benedek G, Bucala R, Offner H. “Near Cure” treatment of severe acute EAE in MIF-1-deficient female and male mice with a bifunctional MHCII-derived molecular construct. Cellular Immunology 2022, 378: 104561. PMID: 35738135, PMCID: PMC9714992, DOI: 10.1016/j.cellimm.2022.104561.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisAcute experimental autoimmune encephalomyelitisDRα1-MOG-35Multiple sclerosisMIF-1EAE scoresMale miceMIF-2Severe diseaseMacrophage migration inhibitory factorClinical EAE scoresMIF-deficient micePeripheral inflammatory cellsMigration inhibitory factorSpinal cord tissueT cell activationSex-dependent differencesEAE severityAutoimmune encephalomyelitisSerum levelsTreatment of WTInflammatory cellsFemale miceClinical signsCord tissueInterleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity
Hailemichael Y, Johnson D, Abdel-Wahab N, Foo W, Bentebibel S, Daher M, Haymaker C, Wani K, Saberian C, Ogata D, Kim S, Nurieva R, Lazar A, Abu-Sbeih H, Fa'ak F, Mathew A, Wang Y, Falohun A, Trinh V, Zobniw C, Spillson C, Burks J, Awiwi M, Elsayes K, Soto L, Melendez B, Davies M, Wargo J, Curry J, Yee C, Lizee G, Singh S, Sharma P, Allison J, Hwu P, Ekmekcioglu S, Diab A. Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity. Cancer Cell 2022, 40: 509-523.e6. PMID: 35537412, PMCID: PMC9221568, DOI: 10.1016/j.ccell.2022.04.004.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeExperimental autoimmune encephalomyelitisInterleukin-6 blockadeInterleukin-6Anti-cytotoxic T-lymphocyte-associated antigen 4T-lymphocyte-associated antigen 4Anti-programmed death-1Experimental autoimmune encephalomyelitis symptomsImmune-related adverse eventsICB-treated patientsPromote tumor immunityAnti-CTLA-4Anti-PD-1Improve tumor controlEffector T cellsT helper 1T helper 17Expression of interleukin-6Chemotactic markersImmunotherapy toxicityReduced Th17Antitumor immunityCheckpoint blockadeTumor controlDeath-1The AIM2 inflammasome is activated in astrocytes during the late phase of EAE
Barclay WE, Aggarwal N, Deerhake ME, Inoue M, Nonaka T, Nozaki K, Luzum NA, Miao EA, Shinohara ML. The AIM2 inflammasome is activated in astrocytes during the late phase of EAE. JCI Insight 2022, 7: e155563. PMID: 35451371, PMCID: PMC9089781, DOI: 10.1172/jci.insight.155563.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisCentral nervous systemInflammasome activationInflammasome-mediated inflammationRole of inflammasomesApoptosis-associated speck-like proteinIL-1β releaseAIM2 inflammasome activationSpeck-like proteinAutoimmune encephalomyelitisEffector cytokinesAutoimmune conditionsIL-18Multiple sclerosisIL-1βDisease peakInflammatory responseSpinal cordMelanoma 2Mouse modelAnimal modelsReporter miceNervous systemMyeloid cellsAIM2 inflammasome
2021
m6A demethylase ALKBH5 controls CD4+ T cell pathogenicity and promotes autoimmunity
Zhou J, Zhang X, Hu J, Qu R, Yu Z, Xu H, Chen H, Yan L, Ding C, Zou Q, Ye Y, Wang Z, Flavell RA, Li HB. m6A demethylase ALKBH5 controls CD4+ T cell pathogenicity and promotes autoimmunity. Science Advances 2021, 7: eabg0470. PMID: 34134995, PMCID: PMC8208713, DOI: 10.1126/sciadv.abg0470.Peer-Reviewed Original ResearchAlkB homolog 5T cell-specific ablationT cellsMRNA stabilityCell-specific ablationMethyladenosine (m<sup>6</sup>A) modificationHomolog 5Pathogenicity of CD4Messenger RNAErasersProtein expressionAdoptive transfer colitisExperimental autoimmune encephalomyelitisHomeostasis of CD4T cell responsesSpecific roleT cell pathogenicityCentral nervous systemDectin-1 limits CNS autoimmunity through a non-canonical pathway
Deerhake M, Danzaki K, Inoue M, Cardakli E, Nonaka T, Aggarwal N, Barclay W, Ji R, Shinohara M. Dectin-1 limits CNS autoimmunity through a non-canonical pathway. The Journal Of Immunology 2021, 206: 96.07-96.07. DOI: 10.4049/jimmunol.206.supp.96.07.Peer-Reviewed Original ResearchExperimental autoimmune encephalomyelitisC-type lectin receptorsCentral nervous systemMultiple sclerosisInnate immunityDectin-1 pathwayCNS autoimmunityEAE severityAutoimmune encephalomyelitisNeuroprotective cytokineNeuroprotective functionNeurologic disordersPathologic roleImmune responseAnimal modelsNervous systemMyeloid cellsOSM receptorNon-canonical pathwayUpregulated expressionOncostatin MLectin receptorsAutoimmunityRNA-seq profilingProtective aspectsPriming of myelin-specific T cells in the absence of dendritic cells results in accelerated development of Experimental Autoimmune Encephalomyelitis
Luu T, Cheung JF, Baccon J, Waldner H. Priming of myelin-specific T cells in the absence of dendritic cells results in accelerated development of Experimental Autoimmune Encephalomyelitis. PLOS ONE 2021, 16: e0250340. PMID: 33891644, PMCID: PMC8064509, DOI: 10.1371/journal.pone.0250340.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisT cell responsesDendritic cellsT cellsMultiple sclerosisCell responsesAutoimmune encephalomyelitisSJL miceProteolipid proteinPro-inflammatory T cell responsesAbsence of DCsImportance of DCsPLP-specific T cellsSpontaneous experimental autoimmune encephalomyelitisMyelin-specific T cellsSelf-reactive T cellsSevere experimental autoimmune encephalomyelitisDendritic cells resultsSelf-reactive CD4Myelin antigensCNS antigensInflammatory CD4Autoimmune diseasesDC deficiencyAnimal modelsDectin-1 limits autoimmune neuroinflammation and promotes myeloid cell-astrocyte crosstalk via Card9-independent expression of Oncostatin M
Deerhake ME, Danzaki K, Inoue M, Cardakli ED, Nonaka T, Aggarwal N, Barclay WE, Ji RR, Shinohara ML. Dectin-1 limits autoimmune neuroinflammation and promotes myeloid cell-astrocyte crosstalk via Card9-independent expression of Oncostatin M. Immunity 2021, 54: 484-498.e8. PMID: 33581044, PMCID: PMC7956124, DOI: 10.1016/j.immuni.2021.01.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesBrainCARD Signaling Adaptor ProteinsCell CommunicationCells, CulturedDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalGalectinsGene Expression RegulationLectins, C-TypeMice, Inbred C57BLMice, KnockoutMultiple SclerosisMyelin-Oligodendrocyte GlycoproteinMyeloid CellsNeurogenic InflammationOncostatin MOncostatin M Receptor beta SubunitPeptide FragmentsReceptors, MitogenSignal TransductionConceptsExperimental autoimmune encephalomyelitisC-type lectin receptorsCentral nervous systemAutoimmune neuroinflammationOncostatin MPro-resolution functionHeat-killed mycobacteriaDectin-1 pathwayDectin-1 ligandsPotential therapeutic targetEAE severityAutoimmune encephalomyelitisNeuroprotective moleculesNeurologic disordersPathologic roleGalectin-9Therapeutic targetTranscription factor NFATNervous systemMyeloid cellsInnate immunityOSM receptorLectin receptorsEnhanced gene expressionNeuroinflammationB-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF
Bakhuraysah MM, Theotokis P, Lee JY, Alrehaili AA, Aui PM, Figgett WA, Azari MF, Abou-Afech JP, Mackay F, Siatskas C, Alderuccio F, Strittmatter SM, Grigoriadis N, Petratos S. B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF. Scientific Reports 2021, 11: 2890. PMID: 33536561, PMCID: PMC7858582, DOI: 10.1038/s41598-021-82346-6.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisEAE-induced miceB cellsB-cell activating factorMeningeal B cellsLumbosacral spinal cordSecretion of immunoglobulinsG0/G1 phaseImmune cell signalingNeurological progressionAutoimmune encephalomyelitisInflammatory infiltrateAxonal dystrophyCentral nervous system myelinSpinal cordRecombinant BAFFActivating factorNgR1Score 1BAFFBAFF stimulationInfiltratesNgR3System myelinG1 phase
2019
A silent agonist of α7 nicotinic acetylcholine receptors modulates inflammation ex vivo and attenuates EAE
Godin J, Roy P, Quadri M, Bagdas D, Toma W, Narendrula-Kotha R, Kishta O, Damaj M, Horenstein N, Papke R, Simard A. A silent agonist of α7 nicotinic acetylcholine receptors modulates inflammation ex vivo and attenuates EAE. Brain Behavior And Immunity 2019, 87: 286-300. PMID: 31874200, PMCID: PMC7604877, DOI: 10.1016/j.bbi.2019.12.014.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsSilent agonistInflammatory painCytokine productionΑ7 nAChRsAnimal modelsAcetylcholine receptorsΑ7 nicotinic acetylcholine receptorNon-neuronal nAChRsExperimental autoimmune encephalomyelitisChronic inflammatory painAnti-inflammatory compoundsInflammation ex vivoChannel openingAutoimmune encephalomyelitisAntagonist mecamylamineMultiple sclerosisInflammatory disordersModulates inflammationMacrophage numbersDisease manifestationsNervous systemReceptor desensitizationInflammationAgonistsPattern Recognition Receptors in Multiple Sclerosis and Its Animal Models
Deerhake ME, Biswas DD, Barclay WE, Shinohara ML. Pattern Recognition Receptors in Multiple Sclerosis and Its Animal Models. Frontiers In Immunology 2019, 10: 2644. PMID: 31781124, PMCID: PMC6861384, DOI: 10.3389/fimmu.2019.02644.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisPattern recognition receptorsMultiple sclerosisCNS autoimmunityAnimal modelsRecognition receptorsIts Animal ModelsNon-immune cellsInnate immune responseProtective functionFunction of PRRsPRR responsesAutoimmune encephalomyelitisImmune responseEndogenous ligandAutoimmunitySclerosisFurther investigationReceptorsDistinct triggersEncephalomyelitisResponse
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