2022
Dectin-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 speciesThe 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
Secreted osteopontin from CD4+ T cells limits acute graft-versus-host disease
Aggarwal N, Deerhake ME, DiPalma D, Shahi SK, Gaggioli MR, Mangalam AK, Shinohara ML. Secreted osteopontin from CD4+ T cells limits acute graft-versus-host disease. Cell Reports 2021, 37: 110170. PMID: 34965439, PMCID: PMC8759344, DOI: 10.1016/j.celrep.2021.110170.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsAcute GVHDHost diseaseMajor target organAcute graftBacteria AkkermansiaGastrointestinal pathologyMouse modelTarget organsFunction of osteopontinCD4Protective rolePotential biomarkersBeneficial effectsEpithelial cellsOPN isoformsMouse mutant modelsGVHDOsteopontinGraftCell deathDiseaseCellsMutant modelsAkkermansiaEmerging roles of Dectin-1 in noninfectious settings and in the CNS
Deerhake ME, Shinohara ML. Emerging roles of Dectin-1 in noninfectious settings and in the CNS. Trends In Immunology 2021, 42: 891-903. PMID: 34489167, PMCID: PMC8487984, DOI: 10.1016/j.it.2021.08.005.Peer-Reviewed Original ResearchConceptsC-type lectin receptorsImmune responseProinflammatory immune responseCentral nervous systemNew therapeutic approachesInnate immune responseMammalian myeloid cellsNeuroprotective responseSterile inflammationNeurologic disordersTherapeutic approachesNervous systemMyeloid cellsFungal infectionsLectin receptorsRecent studiesCurrent understandingResponseInflammationΒ-glucanInfectionSettingImmunologyReceptorsSingle-Cell Transcriptional Heterogeneity of Neutrophils During Acute Pulmonary Cryptococcus neoformans Infection
Deerhake ME, Reyes EY, Xu-Vanpala S, Shinohara ML. Single-Cell Transcriptional Heterogeneity of Neutrophils During Acute Pulmonary Cryptococcus neoformans Infection. Frontiers In Immunology 2021, 12: 670574. PMID: 33995406, PMCID: PMC8116703, DOI: 10.3389/fimmu.2021.670574.Peer-Reviewed Original ResearchConceptsPulmonary Cryptococcus neoformans infectionDistinct neutrophil subsetsCryptococcus neoformans infectionRole of neutrophilsLigand-receptor analysisCytokine gene expressionFirst-line defensePulmonary cryptococcosisNeoformans infectionDendritic cellsNeutrophil subsetsNeutrophil heterogeneityNeutrophil functionImmune cellsCell transcriptional heterogeneityAlveolar macrophagesNeutrophilsFungal infectionsCryptococcus neoformansInfectionSingle-cell transcriptional analysisGene expressionGenerate ROSOxidative stress signatureTranscriptional heterogeneityDectin-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 expressionNeuroinflammation
2020
Functional heterogeneity of alveolar macrophage population based on expression of CXCL2
Xu-Vanpala S, Deerhake ME, Wheaton JD, Parker ME, Juvvadi PR, MacIver N, Ciofani M, Shinohara ML. Functional heterogeneity of alveolar macrophage population based on expression of CXCL2. Science Immunology 2020, 5 PMID: 32769172, PMCID: PMC7717592, DOI: 10.1126/sciimmunol.aba7350.Peer-Reviewed Original ResearchConceptsPulmonary fungal infectionAlveolar macrophagesFungal infectionsAM subpopulationsPharmacological intervention targetPro-inflammatory moleculesLung-resident macrophagesAnti-inflammatory moleculesExpression of CXCL2Strong inflammatory responseAlveolar macrophage populationComplement component 1qDistinct metabolic profilesC1q expressionInterleukin-10Inflammatory responseSentinel cellsPhagocytic capacityMacrophage populationsCXCL2InfectionMetabolic profileIntervention targetsSubpopulationsAM population
2019
Pattern 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
2015
Epigenetic control of intestinal barrier function and inflammation in zebrafish
Marjoram L, Alvers A, Deerhake ME, Bagwell J, Mankiewicz J, Cocchiaro JL, Beerman RW, Willer J, Sumigray KD, Katsanis N, Tobin DM, Rawls JF, Goll MG, Bagnat M. Epigenetic control of intestinal barrier function and inflammation in zebrafish. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 2770-2775. PMID: 25730872, PMCID: PMC4352795, DOI: 10.1073/pnas.1424089112.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsUbiquitin-like proteinEpigenetic controlTumor necrosis factorEpigenetic repressionLoss of functionIntestinal epitheliumPrecise regulationInflammatory bowel diseasePromoter methylationBarrier functionChronic inflammationEpithelial cellsTNF inductionPotent cytokineImmune cell recruitmentIntestinal barrier functionCell sheddingTNFA expressionRing fingerProinflammatory stimuliProper responseExpressionHoming signalsCell recruitment
2013
Inducible mouse models illuminate parameters influencing epigenetic inheritance
Wan M, Gu H, Wang J, Huang H, Zhao J, Kaundal RK, Yu M, Kushwaha R, Chaiyachati BH, Deerhake E, Chi T. Inducible mouse models illuminate parameters influencing epigenetic inheritance. Development 2013, 140: 843-852. PMID: 23325759, PMCID: PMC3557779, DOI: 10.1242/dev.088229.Peer-Reviewed Original ResearchConceptsTransgenerational inheritanceEpigenetic perturbationsModification patternsChromatin modification patternsRepressive chromatin modificationsAberrant epigenetic modificationsTarget gene sequenceMitotic inheritanceChromatin modificationsEpigenetic inheritanceEpigenetic stateMetastable epiallelesEpigenetic modificationsTranscription factorsGene sequencesDNA sequencesEpigenetic programmingTarget genesCOL1A1 locusFetal epigenomeExtraordinary malleabilityPleiotropic effectsInducible mouse modelEpigenomeTransient manipulation
2009
Genetic Analysis of Blood Pressure in 8 Mouse Intercross Populations
Feng M, Deerhake ME, Keating R, Thaisz J, Xu L, Tsaih SW, Smith R, Ishige T, Sugiyama F, Churchill GA, DiPetrillo K. Genetic Analysis of Blood Pressure in 8 Mouse Intercross Populations. Hypertension 2009, 54: 802-809. PMID: 19652078, PMCID: PMC2854560, DOI: 10.1161/hypertensionaha.109.134569.Peer-Reviewed Original ResearchConceptsQuantitative trait lociIntercross populationCausal genesBlood pressure quantitative trait lociExcellent genetic resourcesConserved roleQTL intervalsQTL analysisGenomic regionsMouse genomeTrait lociHuman genomeGenetic resourcesBioinformatics methodsGenetic basisCandidate genesGenetic analysisGenesMultiple crossesGenomeHypertension genesBlood pressureLociMiceBlood pressure regulation