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
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
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