2024
The amalgam of naive CD4+ T cell transcriptional states is reconfigured by helminth infection to dampen the amplitude of the immune response
Even Z, Meli A, Tyagi A, Vidyarthi A, Briggs N, de Kouchkovsky D, Kong Y, Wang Y, Waizman D, Rice T, De Kumar B, Wang X, Palm N, Craft J, Basu M, Ghosh S, Rothlin C. The amalgam of naive CD4+ T cell transcriptional states is reconfigured by helminth infection to dampen the amplitude of the immune response. Immunity 2024, 57: 1893-1907.e6. PMID: 39096910, DOI: 10.1016/j.immuni.2024.07.006.Peer-Reviewed Original ResearchT cell receptorImmune responseNaive CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cellsIFN-IHelminth infectionsNippostrongylus brasiliensis infectionDecreased immune responseType I interferonNaive TT cellsMemory-likeUnrelated antigensTranscriptional changesExtracellular matrixSPF miceCell receptorsI interferonGerm-freeResponse to certain environmental cuesInfectionMiceFunctional changesCell transcriptional statesTranscriptional heterogeneityHow and why eLife selects papers for peer review
Behrens T, Dalal Y, Harper D, Weigel D, Ajijola O, Andreotti A, Araújo S, Banerjee U, Bhargava B, Bi Y, Büchel C, Campelo F, Cardona A, Cheah K, Chen L, Choi M, Colgin L, Cooper J, Cui Q, de Lange F, Desplan C, Dötsch V, El-Deiry W, Franco E, Frank M, Garrett W, Gold J, Hauf S, Huang C, Huguenard J, James D, Kana B, Kapahi P, King A, Kleine-Vehn J, Kornmann B, Liu C, Luo H, Maduke M, Makin T, Marquand A, Marston A, Mistry P, Moses A, Nelson S, Ng T, Ojala P, Perry G, Poirazi P, Postovit L, Ramachandran S, Rasmann S, Rath S, Roiser J, Ron D, Rothlin C, Schoggins J, Schuman M, Shinn-Cunningham B, Shoback D, Smith L, Soldati-Favre D, Stainier D, Sussel L, Swartz K, Taffe M, Taniguchi T, VijayRaghavan K, Walczak A, Wassum K, White R, Wong M, Yan W, Yuen T, Chugh M, Han L, Marei S, Mencia R, Mittal D, Ochola E, Romani F, Yap L. How and why eLife selects papers for peer review. ELife 2024, 13: e100571. PMID: 39041434, PMCID: PMC11265793, DOI: 10.7554/elife.100571.Peer-Reviewed Original ResearchIn the Eyes of the Beholder—New Mertk Knockout Mouse and Re-Evaluation of Phagocytosis versus Anti-Inflammatory Functions of MERTK
Ghosh S, Finnemann S, Vollrath D, Rothlin C. In the Eyes of the Beholder—New Mertk Knockout Mouse and Re-Evaluation of Phagocytosis versus Anti-Inflammatory Functions of MERTK. International Journal Of Molecular Sciences 2024, 25: 5299. PMID: 38791338, PMCID: PMC11121519, DOI: 10.3390/ijms25105299.Peer-Reviewed Original ResearchReceptor tyrosine kinasesFamily of receptor tyrosine kinasesTAM family of receptor tyrosine kinasesEarly-onset photoreceptor degenerationKnockout mouse modelMolecular functionsNegative regulator of inflammationKnockout phenotypesNegative regulatorMouse geneticsRegulation of inflammationMolecular approachesEmbryonic stem cellsAnti-inflammatory functionsRetinal degenerationTyrosine kinasePhotoreceptor degenerationKnockout miceKnockout modelsMouse modelRodent modelsTAM familyMerTK functionStem cellsAllelesApoptotic 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-4EngulfmentPhenotypeTREM2 function in glioblastoma immune microenvironment: Can we distinguish reality from illusion?
Ghosh S, Rothlin C. TREM2 function in glioblastoma immune microenvironment: Can we distinguish reality from illusion? Neuro-Oncology 2024, 26: 840-842. PMID: 38290471, PMCID: PMC11066908, DOI: 10.1093/neuonc/noae019.Peer-Reviewed Original Research
2023
Nmes1 is a novel regulator of mucosal response influencing intestinal healing potential
Hamley M, Leyk S, Casar C, Liebold I, Al Jawazneh A, Lanzloth C, Böttcher M, Haas H, Richardt U, Rothlin C, Jacobs T, Huber S, Adlung L, Pelczar P, Henao‐Mejia J, Bosurgi L. Nmes1 is a novel regulator of mucosal response influencing intestinal healing potential. European Journal Of Immunology 2023, 54: e2350434. PMID: 37971166, DOI: 10.1002/eji.202350434.Peer-Reviewed Original ResearchMucosal healingSchistosoma mansoni infectionCytokines IL-4Innovative therapeutic approachesDifferent intestinal diseasesWound-healing potentialIntestinal damageMucosal responsesMansoni infectionInflamed colonIL-4Intestinal disordersIntestinal diseaseNormal mucosaMurine modelTherapeutic approachesNovel regulatorType 2Advanced stageTherapy efficacyMacrophage responseCell therapyHealing potentialNew targetsIntestinal regeneration
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
2020
Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo
Damisah EC, Hill RA, Rai A, Chen F, Rothlin CV, Ghosh S, Grutzendler J. Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo. Science Advances 2020, 6: eaba3239. PMID: 32637606, PMCID: PMC7319765, DOI: 10.1126/sciadv.aba3239.Peer-Reviewed Original ResearchConceptsCorpse removalPrecise spatiotemporal resolutionApoptotic cell removalReceptor tyrosine kinasesGlial cellsOrchestrated rolesTyrosine kinaseApoptotic bodiesCell deathSpecialized roleCoordinated interactionPhagocytic interactionSingle cellsBrain homeostasisCellsCell removalIntravital optical imagingSpatiotemporal resolutionRole of phagocytesSynchronized fashionKinaseMarked delayRoleHomeostasisAstrocytes
2019
Universal Principled Review: A Community-Driven Method to Improve Peer Review
Krummel M, Blish C, Kuhns M, Cadwell K, Oberst A, Goldrath A, Ansel K, Chi H, O’Connell R, Wherry E, Pepper M, Consortium T, Brodsky I, Chang J, Arron J, Haining N, Bhattacharya D, Anderson M, Rothlin C, Schwab S, Belkaid Y, Molofsky A, Savage P, Mucida D, Iwasaki A, Victora G, Ansel K, Hamerman J, Masopust D, Barton G, Kaech S, Woodruff P, Stetson D, Scharschmidt T, Kedl R, Zúñiga E, Hoffmann A, Williams M, Mayer-Barber K, Shin S, Bensinger S, Lu L, Looney M, Round J, Amigorena S, Yewdell J, Sun J, Harty J. Universal Principled Review: A Community-Driven Method to Improve Peer Review. Cell 2019, 179: 1441-1445. PMID: 31835023, DOI: 10.1016/j.cell.2019.11.029.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
2011
T cell derived Protein S inhibits the activation of Dendritic cells through the TAM receptors Axl and Mer
Silva E, Chan P, Joannas L, Burstyn-Cohen T, Lemke G, Ghosh S, Rothlin C. T cell derived Protein S inhibits the activation of Dendritic cells through the TAM receptors Axl and Mer. Inflammatory Bowel Diseases 2011, 17: s10-s10. DOI: 10.1097/00054725-201112002-00028.Peer-Reviewed Original Research
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