Featured Publications
Tissue-specific modifier alleles determine Mertk loss-of-function traits
Akalu YT, Mercau ME, Ansems M, Hughes LD, Nevin J, Alberto EJ, Liu XN, He LZ, Alvarado D, Keler T, Kong Y, Philbrick WM, Bosenberg M, Finnemann SC, Iavarone A, Lasorella A, Rothlin CV, Ghosh S. Tissue-specific modifier alleles determine Mertk loss-of-function traits. ELife 2022, 11: e80530. PMID: 35969037, PMCID: PMC9433089, DOI: 10.7554/elife.80530.Peer-Reviewed Original ResearchConceptsAnti-tumor immunityKO miceRetinal pigment epitheliumRetinal degenerationPigment epitheliumPro-inflammatory tumor microenvironmentSyngeneic mouse tumor modelsKO mice displayEarly-onset retinal degenerationSevere retinal degenerationMouse tumor modelsFailure of macrophagesKnockout mouse modelPhotoreceptor outer segmentsMouse modelMice displayTumor modelTumor microenvironmentMacrophage phagocytosisReceptor tyrosine kinasesMiceCritical roleDegenerationMerTKImmunityInflammation of the retinal pigment epithelium drives early-onset photoreceptor degeneration in Mertk-associated retinitis pigmentosa
Mercau M, Akalu Y, Mazzoni F, Gyimesi G, Alberto E, Kong Y, Hafler B, Finnemann S, Rothlin C, Ghosh S. Inflammation of the retinal pigment epithelium drives early-onset photoreceptor degeneration in Mertk-associated retinitis pigmentosa. Science Advances 2023, 9: eade9459. PMID: 36662852, PMCID: PMC9858494, DOI: 10.1126/sciadv.ade9459.Peer-Reviewed Original ResearchConceptsRetinal pigment epitheliumEarly-onset photoreceptor degenerationPR degenerationPigment epitheliumPhotoreceptor degenerationMERTK-associated retinitis pigmentosaJAK1/2 inhibitor ruxolitinibMicroglia activationMonocyte infiltrationInhibitor ruxolitinibMouse modelInflammationLoss of functionDefective phagocytosisInflammation drivesRetinitis pigmentosaDegenerationHypomorphic expressionMiceEpitheliumPhagocytosisRuxolitinibPigmentosaSeverity
2023
Age-dependent differences in efferocytosis determine the outcome of opsonophagocytic protection from invasive pathogens
Bee G, Lokken-Toyli K, Yeung S, Rodriguez L, Zangari T, Anderson E, Ghosh S, Rothlin C, Brodin P, Khanna K, Weiser J. Age-dependent differences in efferocytosis determine the outcome of opsonophagocytic protection from invasive pathogens. Immunity 2023, 56: 1255-1268.e5. PMID: 37059107, PMCID: PMC10330046, DOI: 10.1016/j.immuni.2023.03.018.Peer-Reviewed Original ResearchConceptsAge-dependent differencesNeonatal neutrophilsEarly lifeModulation of CD11bCD11b surface expressionAge-dependent susceptibilitySpn infectionPeripheral bloodMore CD11bMouse modelInfection outcomesStreptococcus pneumoniaeNeutrophilsCD11bEfferocytosisSystemic expressionSurface expressionNeonatesOpsonophagocytosisInvasive pathogensOutcomesPopulation levelCD169PathogensExpression
2022
Regulation of bone homeostasis by MERTK and TYRO3
Engelmann J, Zarrer J, Gensch V, Riecken K, Berenbrok N, Luu T, Beitzen-Heineke A, Vargas-Delgado M, Pantel K, Bokemeyer C, Bhamidipati S, Darwish I, Masuda E, Burstyn-Cohen T, Alberto E, Ghosh S, Rothlin C, Hesse E, Taipaleenmäki H, Ben-Batalla I, Loges S. Regulation of bone homeostasis by MERTK and TYRO3. Nature Communications 2022, 13: 7689. PMID: 36509738, PMCID: PMC9744875, DOI: 10.1038/s41467-022-33938-x.Peer-Reviewed Original ResearchConceptsCancer-induced bone lossBone homeostasisBone lossBone-resorbing osteoclastsBone metastasesProlong survivalOsteoanabolic therapyMultiple myelomaLung cancerBone-forming osteoblastsBone massHealthy micePreclinical modelsOsteoblast numberMerTKTyro3Bone formationMicePotent regulatorCell type-specific functionsFine equilibriumBlockadeCancerHomeostasisOsteoblast differentiation
2018
aPKCζ-dependent Repression of Yap is Necessary for Functional Restoration of Irradiated Salivary Glands with IGF-1
Chibly AM, Wong WY, Pier M, Cheng H, Mu Y, Chen J, Ghosh S, Limesand KH. aPKCζ-dependent Repression of Yap is Necessary for Functional Restoration of Irradiated Salivary Glands with IGF-1. Scientific Reports 2018, 8: 6347. PMID: 29679075, PMCID: PMC5910385, DOI: 10.1038/s41598-018-24678-4.Peer-Reviewed Original Research
2017
Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage
Chang CF, Goods BA, Askenase MH, Hammond MD, Renfroe SC, Steinschneider AF, Landreneau MJ, Ai Y, Beatty HE, da Costa LHA, Mack M, Sheth KN, Greer DM, Huttner A, Coman D, Hyder F, Ghosh S, Rothlin CV, Love JC, Sansing LH. Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage. Journal Of Clinical Investigation 2017, 128: 607-624. PMID: 29251628, PMCID: PMC5785262, DOI: 10.1172/jci95612.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAxl Receptor Tyrosine KinaseBrain InjuriesCerebral HemorrhageC-Mer Tyrosine KinaseErythrocytesHematomaHumansImmunity, InnateInflammationMacrophagesMaleMiceMice, Inbred C57BLMice, TransgenicPhagocytosisPhenotypeProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSolubilityTreatment OutcomeConceptsMonocyte-derived macrophagesIntracerebral hemorrhageEryptotic erythrocytesNeurological recoveryHematoma clearanceExperimental intracerebral hemorrhageReceptor tyrosine kinase AXLHuman monocyte-derived macrophagesTyrosine kinase AXLICH onsetFunctional outcomeBrain injuryTissue injurySoluble AxlDynamic phenotypic changesAlternative activationPhenotypic changesMacrophage phenotypeIron depositionMurine brainMacrophage responseRestorative functionEfferocytosisMacrophagesEngulfment of erythrocytesMacrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells
Bosurgi L, Cao YG, Cabeza-Cabrerizo M, Tucci A, Hughes LD, Kong Y, Weinstein JS, Licona-Limon P, Schmid ET, Pelorosso F, Gagliani N, Craft JE, Flavell RA, Ghosh S, Rothlin CV. Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells. Science 2017, 356: 1072-1076. PMID: 28495875, PMCID: PMC5556699, DOI: 10.1126/science.aai8132.Peer-Reviewed Original ResearchConceptsApoptotic cellsTissue repair programChemotaxis genesTissue-resident macrophagesIL-4IL-13Tissue repairPattern recognition receptorsTissue repair genesCell adhesionRepair genesGenetic ablationCytokine-dependent inductionHelminth infectionsRecognition receptorsInduction of colitisGenesBroad repertoireSoluble cytokinesMacrophage functionCellsInductionHost responseEctopic activityInterleukin-4
2016
The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity
Chan PY, Carrera Silva EA, De Kouchkovsky D, Joannas LD, Hao L, Hu D, Huntsman S, Eng C, Licona-Limón P, Weinstein JS, Herbert DR, Craft JE, Flavell RA, Repetto S, Correale J, Burchard EG, Torgerson DG, Ghosh S, Rothlin CV. The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity. Science 2016, 352: 99-103. PMID: 27034374, PMCID: PMC4935984, DOI: 10.1126/science.aaf1358.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAsthmaBlood ProteinsDendritic CellsDisease Models, AnimalGene Knockout TechniquesHost-Parasite InteractionsHumansImmunity, InnateInterleukin-4MiceMice, Inbred C57BLMice, KnockoutNippostrongylusProtein SPyroglyphidaeReceptor Protein-Tyrosine KinasesStrongylida InfectionsT-LymphocytesConceptsType 2 immunityType 2 responsesType 2 cytokinesHuman dendritic cellsInnate immune cellsDendritic cellsAllergic diseasesImmune cellsT cellsAdaptive immunityInterleukin-4Host responseFunctional neutralizationGenetic ablationReceptor tyrosine kinasesImmunityProtective functionTyro3Tyrosine kinaseNegative regulatorPROS1CellsResponseCytokinesDisease
2014
Targeting aPKC disables oncogenic signaling by both the EGFR and the proinflammatory cytokine TNFα in glioblastoma
Kusne Y, Carrera-Silva EA, Perry AS, Rushing EJ, Mandell EK, Dietrich JD, Errasti AE, Gibbs D, Berens ME, Loftus JC, Hulme C, Yang W, Lu Z, Aldape K, Sanai N, Rothlin CV, Ghosh S. Targeting aPKC disables oncogenic signaling by both the EGFR and the proinflammatory cytokine TNFα in glioblastoma. Science Signaling 2014, 7: ra75. PMID: 25118327, PMCID: PMC4486020, DOI: 10.1126/scisignal.2005196.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisDrug Delivery SystemsEnzyme-Linked Immunosorbent AssayEpidermal Growth FactorErbB ReceptorsErlotinib HydrochlorideFlow CytometryFluorescent Antibody TechniqueGlioblastomaHumansImmunoblottingImmunohistochemistryImmunoprecipitationKaplan-Meier EstimateMiceNF-kappa BParacrine CommunicationProtein Kinase CQuinazolinesReverse Transcriptase Polymerase Chain ReactionSignal TransductionTumor Necrosis Factor-alphaConceptsAtypical protein kinase CEpidermal growth factor receptorEGFR kinase inhibitorsHuman glioblastoma tumor cellsReceptor tyrosine kinasesProtein kinase CTNFα-dependent activationKinase inhibitorsTranscription factor nuclear factor κBGlioblastoma tumor cellsGrowth factor receptorKinase activityMolecular approachesTyrosine kinaseKinase CNuclear factor κBFactor receptorGlioblastoma microenvironmentFactor κBProinflammatory cytokine TNFαAbundanceTumor necrosis factorGlioblastoma therapyTumor growthGrade IV glioblastomaTyro3, Axl, and Mertk Receptor Signaling in Inflammatory Bowel Disease and Colitis-associated Cancer
Rothlin CV, Leighton JA, Ghosh S. Tyro3, Axl, and Mertk Receptor Signaling in Inflammatory Bowel Disease and Colitis-associated Cancer. Inflammatory Bowel Diseases 2014, 20: 1472-1480. PMID: 24846720, PMCID: PMC4343000, DOI: 10.1097/mib.0000000000000050.BooksConceptsInflammatory bowel diseaseBowel diseaseImmune responseT-cell-dependent adaptive immune responsesApoptotic cellsReceptor tyrosine kinasesProinflammatory cytokine productionSuppression of inflammationAdaptive immune responsesInnate immune responseTAM receptor tyrosine kinasesPotent therapeutic opportunityDisease remissionTyrosine kinaseIntestinal inflammationCytokine productionInflammatory responseLigand Gas6Potent negative regulatorTherapeutic opportunitiesGenetic ablationInflammationProtein SReceptor signalingSuccessful managementLocal Translation and Retrograde Axonal Transport of CREB Regulates IL-6-Induced Nociceptive Plasticity
Melemedjian OK, Tillu DV, Moy JK, Asiedu MN, Mandell EK, Ghosh S, Dussor G, Price TJ. Local Translation and Retrograde Axonal Transport of CREB Regulates IL-6-Induced Nociceptive Plasticity. Molecular Pain 2014, 10: 1744-8069-10-45. PMID: 24993495, PMCID: PMC4091745, DOI: 10.1186/1744-8069-10-45.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonal TransportBrain-Derived Neurotrophic FactorCells, CulturedColchicineCREB-Binding ProteinDisease Models, AnimalGanglia, SpinalGene Expression RegulationInterleukin-6MaleMiceMice, Inbred ICRNociceptive PainNocodazoleProtein TransportQuinazolinonesSciatic NerveSensory Receptor CellsTubulin ModulatorsConceptsCyclic AMP response element binding proteinDorsal root gangliaInterleukin-6Retrograde axonal transportNerve growth factorHyperalgesic primingMechanical hypersensitivityAxonal transportNociceptive plasticitySensory neuronsRetrograde transportExpression of BDNFPrimary sensory neuronsExpression of CREBHr post injectionIL-6 treatmentAxonal traffickingActivity-dependent translationAMP response element binding proteinResponse element-binding proteinCREB DNA bindingIntrathecal injectionHindpaw injectionNociceptive sensitizationInflammatory model
2013
Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice
Kusne Y, Goldberg EL, Parker SS, Hapak SM, Maskaykina IY, Chew WM, Limesand KH, Brooks HL, Price TJ, Sanai N, Nikolich-Zugich J, Ghosh S. Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice. GeroScience 2013, 36: 199-212. PMID: 23949159, PMCID: PMC3889877, DOI: 10.1007/s11357-013-9572-5.Peer-Reviewed Original ResearchConceptsSystemic administrationMTOR inhibitorsImproved health spanAdult-born neuronsHealth spanEffects of chronicNeural progenitorsAdult neural stem cellsMTOR inhibitor rapamycinInhibition of mTORPotential adverse effectsAdult neural progenitorsNeural stem cellsSystemic treatmentDendate gyrusMouse hippocampusSubventricular regionOrgan functionMetforminBehavioral healthInhibitor rapamycinAdverse effectsPharmacological inhibitorsMTORRapamycinParadoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer
Bosurgi L, Bernink JH, Cuevas V, Gagliani N, Joannas L, Schmid ET, Booth CJ, Ghosh S, Rothlin CV. Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 13091-13096. PMID: 23878224, PMCID: PMC3740859, DOI: 10.1073/pnas.1302507110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAxl Receptor Tyrosine KinaseAzoxymethaneC-Mer Tyrosine KinaseColitisColonColonic NeoplasmsCytokinesDextran SulfateFemaleFlow CytometryGene ExpressionMacrophagesMaleMiceMice, Inbred StrainsMice, KnockoutMucous MembraneNeutrophilsPhagocytosisProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesReverse Transcriptase Polymerase Chain ReactionSignal TransductionConceptsTumor-promoting environmentMer receptor tyrosine kinaseSystemic anticancer therapyDextran sulfate sodiumAnticancer therapyIntestinal lamina propriaAnti-inflammatory functionsInflammation-associated cancerPotential adverse effectsInflammatory signatureDendritic cellsSulfate sodiumIntestinal macrophagesProinflammatory cytokinesLamina propriaColon cancerTherapeutic targetingOncogenic roleMer inhibitorsApoptotic neutrophilsAxlMultiple cancer hallmarksReceptor tyrosine kinasesTumor cellsAdverse effectsT Cell-Derived Protein S Engages TAM Receptor Signaling in Dendritic Cells to Control the Magnitude of the Immune Response
Silva E, Chan PY, Joannas L, Errasti AE, Gagliani N, Bosurgi L, Jabbour M, Perry A, Smith-Chakmakova F, Mucida D, Cheroutre H, Burstyn-Cohen T, Leighton JA, Lemke G, Ghosh S, Rothlin CV. T Cell-Derived Protein S Engages TAM Receptor Signaling in Dendritic Cells to Control the Magnitude of the Immune Response. Immunity 2013, 39: 160-170. PMID: 23850380, PMCID: PMC4017237, DOI: 10.1016/j.immuni.2013.06.010.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsCells, CulturedColitisCytokinesDendritic CellsFlow CytometryGene ExpressionHumansImmunoblottingLymphocyte ActivationMiceMice, KnockoutMice, TransgenicProtein SReceptor Protein-Tyrosine KinasesReverse Transcriptase Polymerase Chain ReactionSignal TransductionT-LymphocytesConceptsImmune responseDC activationProtein STAM receptor signalingDendritic cell activationExaggerated immune responseTAM receptor tyrosine kinasesDendritic cellsChronic inflammationCostimulatory moleculesImmune homeostasisAdaptive immunityCell activationInnate immunityGenetic ablationReceptor tyrosine kinasesReceptor signalingImmune defenseNegative feedback mechanismMouse TImmunityActivationTyrosine kinaseCellsPROS1mTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK
Melemedjian OK, Khoutorsky A, Sorge RE, Yan J, Asiedu MN, Valdez A, Ghosh S, Dussor G, Mogil JS, Sonenberg N, Price TJ. mTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK. Pain 2013, 154: 1080-1091. PMID: 23607966, PMCID: PMC3742001, DOI: 10.1016/j.pain.2013.03.021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDown-RegulationEnzyme ActivationFeedback, PhysiologicalInsulin Receptor Substrate ProteinsMaleMAP Kinase Signaling SystemMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLMice, Inbred ICRMultiprotein ComplexesPainRatsRats, Sprague-DawleySensory Receptor CellsSirolimusTOR Serine-Threonine KinasesConceptsSpontaneous painMechanical hypersensitivitySensory neuronsDevelopment of painPotential treatment optionSensory neuron sensitizationRapamycin complex 1 (mTORC1) inhibitorsExtracellular signal-regulated kinase (ERK) pathwaySignal-regulated kinase pathwaySuppression of S6K1Chronic treatmentPain conditionsPain therapeuticsTransplant rejectionAdenosine monophosphate-activated protein kinase (AMPK) activatorProtein kinase activatorsTreatment optionsAntidiabetic drugsPainSensory hypersensitivityMTOR pathwayNegative feedback loopCertain cancersMammalian targetMTORC1 inhibitionBDNF Regulates Atypical PKC at Spinal Synapses to Initiate and Maintain a Centralized Chronic Pain State
Melemedjian OK, Tillu DV, Asiedu MN, Mandell EK, Moy JK, Blute VM, Taylor CJ, Ghosh S, Price TJ. BDNF Regulates Atypical PKC at Spinal Synapses to Initiate and Maintain a Centralized Chronic Pain State. Molecular Pain 2013, 9: 1744-8069-9-12. PMID: 23510079, PMCID: PMC3608966, DOI: 10.1186/1744-8069-9-12.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain-Derived Neurotrophic FactorCalcium-Calmodulin-Dependent Protein Kinase Type 2Cerebral CortexChronic PainEukaryotic Initiation Factor-4FExtracellular Signal-Regulated MAP KinasesMaleMAP Kinase Signaling SystemMiceMice, Inbred ICRMitogen-Activated Protein Kinase KinasesModels, BiologicalPhosphorylationPosterior Horn CellsProtein BiosynthesisProtein Kinase CProtein TransportSynapsesTime FactorsTOR Serine-Threonine KinasesConceptsChronic pain statesPain statesPersistent nociceptive sensitizationSpinal synapsesChronic painNociceptive sensitizationPotential therapeutic targetImportant medical problemNeurotrophic factorBDNF regulationPersistent sensitizationBDNFTherapeutic targetMedical problemsPainNovel therapeuticsEssential mediatorSensitizationPermanent reversalSynapsesMolecular linkPKMζKey regulator
2011
Spinal Protein Kinase M ζ Underlies the Maintenance Mechanism of Persistent Nociceptive Sensitization
Asiedu MN, Tillu DV, Melemedjian OK, Shy A, Sanoja R, Bodell B, Ghosh S, Porreca F, Price TJ. Spinal Protein Kinase M ζ Underlies the Maintenance Mechanism of Persistent Nociceptive Sensitization. Journal Of Neuroscience 2011, 31: 6646-6653. PMID: 21543593, PMCID: PMC3090264, DOI: 10.1523/jneurosci.6286-10.2011.Peer-Reviewed Original ResearchConceptsLate long-term potentiationInterleukin-6Intraplantar injectionPersistent nociceptive sensitizationIntrathecal injectionNociceptive sensitizationResolution of hypersensitivitySpinal dorsal hornClinical pain disordersProtein kinase M ζLong-term potentiationAllodynic statePlantar incisionDorsal hornPain pathwaysPain statesAgonist injectionPain disordersAgonist DHPGNocifensive behaviorNocifensive responsesPKMζ inhibitorSpinal cordAllodyniaTherapeutic benefit
2010
Telomere-independent Rap1 is an IKK adaptor and regulates NF-κB-dependent gene expression
Teo H, Ghosh S, Luesch H, Ghosh A, Wong ET, Malik N, Orth A, de Jesus P, Perry AS, Oliver JD, Tran NL, Speiser LJ, Wong M, Saez E, Schultz P, Chanda SK, Verma IM, Tergaonkar V. Telomere-independent Rap1 is an IKK adaptor and regulates NF-κB-dependent gene expression. Nature Cell Biology 2010, 12: 758-767. PMID: 20622870, DOI: 10.1038/ncb2080.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBlotting, WesternCell LineCell Line, TumorChromatin ImmunoprecipitationChromatography, GelHeLa CellsHumansI-kappa B KinaseImmunohistochemistryImmunoprecipitationKaplan-Meier EstimateMiceNF-kappa BPhosphorylationPolymerase Chain ReactionProtein BindingRNA, Small InterferingShelterin ComplexTelomere-Binding ProteinsTissue Array Analysis
2008
Instructive role of aPKCζ subcellular localization in the assembly of adherens junctions in neural progenitors
Ghosh S, Marquardt T, Thaler JP, Carter N, Andrews SE, Pfaff SL, Hunter T. Instructive role of aPKCζ subcellular localization in the assembly of adherens junctions in neural progenitors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 335-340. PMID: 18162555, PMCID: PMC2224213, DOI: 10.1073/pnas.0705713105.Peer-Reviewed Original ResearchConceptsAdherens junctionsNeural progenitorsNeural tubeApical-basal polarityCell fate determinantsNeuronal precursorsApical adherens junctionsApical membranePKCzeta/lambdaCell-cell adhesionChicken neural tubeStem cell proliferationPostmitotic neuronal precursorsAsymmetric inheritanceApical assemblyFate determinantsAsymmetric localizationNeural stem cell proliferationSubcellular compartmentalizationSubcellular localizationNeural stem cellsKinase activityInstructive signalsNeurogenic divisionsInstructive role
2007
TAM Receptors Are Pleiotropic Inhibitors of the Innate Immune Response
Rothlin CV, Ghosh S, Zuniga EI, Oldstone MB, Lemke G. TAM Receptors Are Pleiotropic Inhibitors of the Innate Immune Response. Cell 2007, 131: 1124-1136. PMID: 18083102, DOI: 10.1016/j.cell.2007.10.034.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxl Receptor Tyrosine KinaseC-Mer Tyrosine KinaseDendritic CellsGene Expression RegulationImmunity, InnateInflammationMiceMice, KnockoutOncogene ProteinsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesReceptor, Interferon alpha-betaSignal TransductionSTAT1 Transcription FactorSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsToll-Like ReceptorsUbiquitinationConceptsToll-like receptorsDendritic cellsImmune responseChronic inflammatory milieuInnate immune responseTAM receptor tyrosine kinasesRapid inflammatory responseType I interferon receptorCytokine-dependent activationTAM inhibitionTLR inductionInflammatory milieuInflammatory responseProinflammatory pathwaysTAM receptorsTLR signalingPleiotropic inhibitorInflammationReceptor tyrosine kinasesTranscription factor STAT1Interferon receptorEssential stimulatorReceptorsTyrosine kinaseTAM system