2024
Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages
Liebold I, Al Jawazneh A, Casar C, Lanzloth C, Leyk S, Hamley M, Wong M, Kylies D, Gräfe S, Edenhofer I, Aranda-Pardos I, Kriwet M, Haas H, Krause J, Hadjilaou A, Schromm A, Richardt U, Eggert P, Tappe D, Weidemann S, Ghosh S, Krebs C, A-Gonzalez N, Worthmann A, Lohse A, Huber S, Rothlin C, Puelles V, Jacobs T, Gagliani N, Bosurgi L. Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages. Science 2024, 384: eabo7027. PMID: 38574142, DOI: 10.1126/science.abo7027.Peer-Reviewed Original ResearchConceptsApoptotic neutrophilsApoptotic cellsIL-4-induced gene expressionUptake of apoptotic neutrophilsApoptotic cell clearanceCell lineage identityResponse to IL-4Cell identityEfferocytic macrophagesPhagocytic receptorsGene expressionLineage identityCell clearanceApoptotic hepatocytesHeterogeneous cellsCellsMouse modelT cellsParasite-induced pathologyIL-4HepatocytesMacrophagesInterleukin-4EngulfmentPhenotype
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 differentiationTissue-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 roleDegenerationMerTKImmunity
2021
Decoding Cell Death: From a Veritable Library of Babel to Vade Mecum?
Hughes LD, Wang Y, Meli AP, Rothlin CV, Ghosh S. Decoding Cell Death: From a Veritable Library of Babel to Vade Mecum? Annual Review Of Immunology 2021, 39: 791-817. PMID: 33902311, DOI: 10.1146/annurev-immunol-102819-072601.Peer-Reviewed Original Research
2017
Macrophage 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
2015
TAM Receptor Signaling in Immune Homeostasis
Rothlin CV, Carrera-Silva EA, Bosurgi L, Ghosh S. TAM Receptor Signaling in Immune Homeostasis. Annual Review Of Immunology 2015, 33: 1-37. PMID: 25594431, PMCID: PMC4491918, DOI: 10.1146/annurev-immunol-032414-112103.BooksConceptsImmune homeostasisTAM receptor signalingFunction of TAMsResolution of inflammationInnate immune responseTAM receptor tyrosine kinasesImmune settingsAutoimmune diseasesImmune responseInfectious diseasesVascular integrityReceptor tyrosine kinasesReceptor signalingDiseaseApoptotic cellsTyrosine kinaseNegative regulationRecent studiesFunctional importanceHomeostasisEssential roleInflammationCancerAxlMerTK
2001
α10: A determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells
Elgoyhen A, Vetter D, Katz E, Rothlin C, Heinemann S, Boulter J. α10: A determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 3501-3506. PMID: 11248107, PMCID: PMC30682, DOI: 10.1073/pnas.051622798.Peer-Reviewed Original ResearchConceptsHair cellsMechanosensory hair cellsCholinergic receptor functionAgonist-mediated desensitizationHair cell functionAlpha9 nAChREfferent modulationHeteromeric nAChRsAlpha9alpha10 nAChRsPharmacological profileBiphasic responseMammalian vestibularReceptor functionAlpha10 subunitsNAChRsCell functionAlpha9Xenopus laevis oocytesCurrent-voltage relationshipVertebrate hair cellsSubunit geneLaevis oocytesAlpha10CellsAlpha9alpha10
2000
Block of the α9 nicotinic receptor by ototoxic aminoglycosides
Rothlin C, Katz E, Verbitsky M, Vetter D, Heinemann S, Elgoyhen A. Block of the α9 nicotinic receptor by ototoxic aminoglycosides. Neuropharmacology 2000, 39: 2525-2532. PMID: 11044724, DOI: 10.1016/s0028-3908(00)00056-3.Peer-Reviewed Original ResearchConceptsAlpha9 nicotinic acetylcholine receptorConcentration of acetylcholineNicotinic acetylcholine receptorsOrgan of CortiOuter hair cellsConcentration-dependent mannerEfferent functionCholinergic receptorsOtotoxic aminoglycosidesNicotinic receptorsAcetylcholine receptorsNon-competitive typeAcetylcholineHair cellsAminoglycosidesGentamicinXenopus laevis oocytesReceptorsAminoglycoside antibioticsReversible actionAlpha9Rank orderPresent studyAntagonistic effectLaevis oocytesMixed nicotinic–muscarinic properties of the α9 nicotinic cholinergic receptor
Verbitsky M, Rothlin C, Katz E, Elgoyhen A. Mixed nicotinic–muscarinic properties of the α9 nicotinic cholinergic receptor. Neuropharmacology 2000, 39: 2515-2524. PMID: 11044723, DOI: 10.1016/s0028-3908(00)00124-6.Peer-Reviewed Original ResearchConceptsOuter hair cellsCholinergic receptorsCholinergic compoundsAlpha9 nicotinic acetylcholine receptorHigh ACh concentrationsNicotinic cholinergic receptorsWeak partial agonistNicotinic acetylcholine receptorsCochlear outer hair cellsAgonist-evoked currentsAlpha9 receptorMuscarinic agonistsMaximal responseAcetylcholine receptorsPartial agonistACh concentrationPharmacological propertiesHair cellsReceptorsXenopus laevis oocytesAcetylcholineNative receptorAgonistsCompetitive typeLaevis oocytesHigh calcium permeability and calcium block of the α9 nicotinic acetylcholine receptor
Katz E, Verbitsky M, Rothlin C, Vetter D, Heinemann S, Elgoyhen A. High calcium permeability and calcium block of the α9 nicotinic acetylcholine receptor. Hearing Research 2000, 141: 117-128. PMID: 10713500, DOI: 10.1016/s0378-5955(99)00214-2.Peer-Reviewed Original ResearchConceptsOuter hair cellsAlpha9 receptorNicotinic acetylcholine receptorsAcetylcholine receptorsAlpha9 nicotinic acetylcholine receptorΑ9 nicotinic acetylcholine receptorHair cellsOlivocochlear efferent fibersHigh calcium permeabilityAuditory nerve fiber activityNerve fiber activityEfferent fibersCholinergic receptorsOlivocochlear fibersVoltage-dependent mannerSynaptic transmissionCalcium permeabilityInhibitory synapseFiber activityReceptorsXenopus laevis oocytesMonovalent currentsLaevis oocytesSynapseCalcium block
1999
The α9 Nicotinic Acetylcholine Receptor Shares Pharmacological Properties with Type A γ-Aminobutyric Acid, Glycine, and Type 3 Serotonin Receptors
Rothlin C, Katz E, Verbitsky M, Elgoyhen A. The α9 Nicotinic Acetylcholine Receptor Shares Pharmacological Properties with Type A γ-Aminobutyric Acid, Glycine, and Type 3 Serotonin Receptors. Molecular Pharmacology 1999, 55: 248-254. PMID: 9927615, DOI: 10.1124/mol.55.2.248.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAnimalsBariumBicucullineCalciumChelating AgentsDNA, ComplementaryEgtazic AcidFemaleGABA AntagonistsGlycineGlycine AgentsIndolesMembrane PotentialsOocytesReceptors, GABA-AReceptors, GlycineReceptors, NicotinicReceptors, SerotoninReceptors, Serotonin, 5-HT3Recombinant Fusion ProteinsSerotoninSerotonin AntagonistsStrychnineTropisetronXenopus laevisConceptsPharmacological propertiesGamma-aminobutyric acid receptor antagonist bicucullineAlpha9 nicotinic acetylcholine receptorACh-evoked currentsAgonist maximal responseType 3 serotonin receptorReceptor antagonist bicucullineGlycinergic antagonist strychnineGamma-aminobutyric acidNicotinic acetylcholine receptorsSimilar pharmacological propertiesCochlear outer hair cellsOuter hair cellsConcentration-dependent mannerCys-loop familyAlpha9 nAChRAntagonist bicucullineAntagonist strychnineCholinergic receptorsΓ-aminobutyric acidCys-loop receptorsSerotonin receptorsMaximal responseAcetylcholine receptorsHair cells