2025
Cold and hot fibrosis define clinically distinct cardiac pathologies
Miyara S, Adler M, Umansky K, Häußler D, Bassat E, Divinsky Y, Elkahal J, Kain D, Lendengolts D, Flores R, Bueno-Levy H, Golani O, Shalit T, Gershovits M, Weizman E, Genzelinakh A, Kimchi D, Shakked A, Zhang L, Wang J, Baehr A, Petrover Z, Sarig R, Dorn T, Moretti A, Saez-Rodriguez J, Kupatt C, Tanaka E, Medzhitov R, Krüger A, Mayo A, Alon U, Tzahor E. Cold and hot fibrosis define clinically distinct cardiac pathologies. Cell Systems 2025, 16: 101198. PMID: 39970910, PMCID: PMC11922821, DOI: 10.1016/j.cels.2025.101198.Peer-Reviewed Original ResearchConceptsHeart failureMyocardial infarctionAutocrine growth factor loopsUnmet medical needCardiac fibrosisNeutralizing antibodiesReduced fibrosisTreatment strategiesMyofibroblast proliferationAcute MIFibrosis post-MICardiac pathologyFibrosisTherapeutic approachesPost-MIChronic injuryMyofibroblastsMedical needFactor loops
2024
Confronting risks of mirror life
Adamala K, Agashe D, Belkaid Y, Bittencourt D, Cai Y, Chang M, Chen I, Church G, Cooper V, Davis M, Devaraj N, Endy D, Esvelt K, Glass J, Hand T, Inglesby T, Isaacs F, James W, Jones J, Kay M, Lenski R, Liu C, Medzhitov R, Nicotra M, Oehm S, Pannu J, Relman D, Schwille P, Smith J, Suga H, Szostak J, Talbot N, Tiedje J, Venter J, Winter G, Zhang W, Zhu X, Zuber M. Confronting risks of mirror life. Science 2024, 386: 1351-1353. PMID: 39666824, DOI: 10.1126/science.ads9158.Peer-Reviewed Original ResearchAdverse Food Reactions: Physiological and Ecological Perspectives
Korn L, Kutyavin V, Bachtel N, Medzhitov R. Adverse Food Reactions: Physiological and Ecological Perspectives. Annual Review Of Nutrition 2024, 44: 155-178. PMID: 38724028, DOI: 10.1146/annurev-nutr-061021-022909.Peer-Reviewed Original ResearchEvolutionary Medicine
Stearns S, Medzhitov R. Evolutionary Medicine. 2024 DOI: 10.1093/oso/9780192871978.001.0001.Peer-Reviewed Original ResearchRisk of metastasisPlacental invasionSolid tumorsEvolution of reproductionMental disordersAdaptive therapyPublic healthVaccine developmentEvolution of agingSick personEvolutionary historyEvolutionary insightsPhage therapyPathogen emergenceIndependent evolutionEvolutionary hypothesesHealthEvolutionary aspectsTherapyCancerDiseaseEvolutionary medicineMedical researchChildbirthMacrophages restrain pathological interferon responses during viral respiratory infection
Rodriguez-Morales P, Hoagland D, Mann A, Yu S, Lai A, Baez Vazquez A, Medzhitov R, Franklin R. Macrophages restrain pathological interferon responses during viral respiratory infection. The Journal Of Immunology 2024, 212: 0536_5144-0536_5144. DOI: 10.4049/jimmunol.212.supp.0536.5144.Peer-Reviewed Original ResearchIFN-I productionOncostatin MBlockade of IFN-I signalingViral stimuliEpithelial cellsIFN-IOSM-deficient miceViral respiratory infectionsTriggered by infectionInflammation-induced pathologyLung epithelial cellsIFN-I responseIFN-I signalingRegulation of inflammationType I interferonPoly(I:CAcute blockadeCytokine oncostatin MRespiratory infectionsUncontrolled inflammationInflammatory responseI interferonInterferon responseRespiratory tractMiceProteostasis maintenance by macrophage trogocytosis
Kimura Y, Philip N, Chavan A, Medzhitov R. Proteostasis maintenance by macrophage trogocytosis. The Journal Of Immunology 2024, 212: 1318_4183-1318_4183. DOI: 10.4049/jimmunol.212.supp.1318.4183.Peer-Reviewed Original ResearchStressed cellsProtein aggregationCellular fitnessMaintenance of cellular fitnessEndoplasmic reticulum stress response pathwayMembrane-associated isoformStress response pathwaysProtein degradation pathwaysDNA repair programsCellular stress responseRemoval of protein aggregatesProtein aggregate accumulationProteostasis maintenanceChaperone inductionHomeostasis in vivoProtein misfoldingResponse pathwaysAbstract CellsCell-to-cell interactionsProteostasisStress responseDNA damageTransferred to macrophagesAggregate accumulationProteinExploring new perspectives in immunology
Medzhitov R, Iwasaki A. Exploring new perspectives in immunology. Cell 2024, 187: 2079-2094. PMID: 38670066, DOI: 10.1016/j.cell.2024.03.038.Peer-Reviewed Original ResearchMechanosensing regulates tissue repair program in macrophages
Meizlish M, Kimura Y, Pope S, Matta R, Kim C, Philip N, Meyaard L, Gonzalez A, Medzhitov R. Mechanosensing regulates tissue repair program in macrophages. Science Advances 2024, 10: eadk6906. PMID: 38478620, PMCID: PMC10936955, DOI: 10.1126/sciadv.adk6906.Peer-Reviewed Original ResearchConceptsExtracellular matrixRegulate chromatin accessibilityTissue repair programGene expression programsCytoskeletal dynamicsChromatin accessibilityAmoeboid migrationCytoskeletal remodelingBiochemical signalsTissue homeostasisExpression programsColony-stimulating factor-1Tissue-resident macrophagesFactor 1MechanosensingRegulating tissue repairTissue integrityMacrophagesTissueThree-dimensional environmentRepair programHomeostasisNutrient-derived signals regulate eosinophil adaptation to the small intestine
Kutyavin V, Korn L, Medzhitov R. Nutrient-derived signals regulate eosinophil adaptation to the small intestine. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2316446121. PMID: 38271336, PMCID: PMC10835075, DOI: 10.1073/pnas.2316446121.Peer-Reviewed Original ResearchConceptsRetinoic acid signalingCrypt-villus axisLocalization signalTissue-specific adaptationsAcid signalingAmino acidsFunctional significanceTranscriptional signatureHomeostatic conditionsSmall intestineTissue microenvironmentType 2 immunityPurified amino acidsSignalAccumulationEffector cellsBone marrowIL-5Eosinophil accumulationSubpopulationsIntestineEffectorAdaptationHigh-protein diet
2023
Characterization of behavioral avoidance to a food allergen in different strains of mice
Lima B, Cullen J, de Paula Carvalho L, Bober J, Florsheim E, Medzhitov R, Dietrich M. Characterization of behavioral avoidance to a food allergen in different strains of mice. Brain Behavior And Immunity 2023, 114: 71. DOI: 10.1016/j.bbi.2024.01.204.Peer-Reviewed Original ResearchOn developmental programming of the immune system
Hong J, Medzhitov R. On developmental programming of the immune system. Trends In Immunology 2023, 44: 877-889. PMID: 37852863, DOI: 10.1016/j.it.2023.09.004.Peer-Reviewed Original ResearchDistinguishing features of long COVID identified through immune profiling
Klein J, Wood J, Jaycox J, Dhodapkar R, Lu P, Gehlhausen J, Tabachnikova A, Greene K, Tabacof L, Malik A, Silva Monteiro V, Silva J, Kamath K, Zhang M, Dhal A, Ott I, Valle G, Peña-Hernández M, Mao T, Bhattacharjee B, Takahashi T, Lucas C, Song E, McCarthy D, Breyman E, Tosto-Mancuso J, Dai Y, Perotti E, Akduman K, Tzeng T, Xu L, Geraghty A, Monje M, Yildirim I, Shon J, Medzhitov R, Lutchmansingh D, Possick J, Kaminski N, Omer S, Krumholz H, Guan L, Dela Cruz C, van Dijk D, Ring A, Putrino D, Iwasaki A. Distinguishing features of long COVID identified through immune profiling. Nature 2023, 623: 139-148. PMID: 37748514, PMCID: PMC10620090, DOI: 10.1038/s41586-023-06651-y.Peer-Reviewed Original ResearchConceptsLong COVIDSARS-CoV-2Infection syndromeExaggerated humoral responseSoluble immune mediatorsEpstein-Barr virusPost-exertional malaiseCross-sectional studyHigher antibody responseImmune mediatorsImmune phenotypingImmune profilingHumoral responseAntibody responseLymphocyte populationsCOVID statusUnbiased machineCortisol levelsLC statusRelevant biomarkersViral pathogensSyndromeCOVIDFuture studiesBiological featuresTissue Biology: In Search of a New Paradigm
Adler M, Chavan A, Medzhitov R. Tissue Biology: In Search of a New Paradigm. Annual Review Of Cell And Developmental Biology 2023, 39: 67-89. PMID: 37607470, DOI: 10.1146/annurev-cellbio-120420-113830.Peer-Reviewed Original ResearchImmune sensing of food allergens promotes avoidance behaviour
Florsheim E, Bachtel N, Cullen J, Lima B, Godazgar M, Carvalho F, Chatain C, Zimmer M, Zhang C, Gautier G, Launay P, Wang A, Dietrich M, Medzhitov R. Immune sensing of food allergens promotes avoidance behaviour. Nature 2023, 620: 643-650. PMID: 37437602, PMCID: PMC10432274, DOI: 10.1038/s41586-023-06362-4.Peer-Reviewed Original ResearchConceptsMast cellsImmune systemBALB/c miceAllergen-specific IgEDifferentiation factor 15Behavioral modificationAllergen avoidanceAllergic sensitizationAllergic inflammationFood allergyTractus solitariusC miceCysteinyl leukotrienesParabrachial nucleusAllergen ingestionE antibodiesCentral amygdalaFactor 15Mouse modelFood allergensBrain areasImmune sensingAvoidance behaviorAversive stimuliGenetic backgroundEmergence of division of labor in tissues through cell interactions and spatial cues
Adler M, Moriel N, Goeva A, Avraham-Davidi I, Mages S, Adams T, Kaminski N, Macosko E, Regev A, Medzhitov R, Nitzan M. Emergence of division of labor in tissues through cell interactions and spatial cues. Cell Reports 2023, 42: 112412. PMID: 37086403, PMCID: PMC10242439, DOI: 10.1016/j.celrep.2023.112412.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingMost cell typesCell-type populationsCell-cell interactionsDistinguishable expression patternsCell population levelSpatial transcriptomics dataCell interactionsLigand-receptor networkMulticellular organismsTranscriptomic dataRNA sequencingInstructive signalsExpression patternsSpecialist cellsCell typesIndividual cellsDivision of laborMultiple functionsTissue environmentSame cellsDifferent functionsPopulation levelCellsDivisionModes of type 2 immune response initiation
Kopp E, Agaronyan K, Licona-LimĂłn I, Nish S, Medzhitov R. Modes of type 2 immune response initiation. Immunity 2023, 56: 687-694. PMID: 37044059, DOI: 10.1016/j.immuni.2023.03.015.Peer-Reviewed Original ResearchAn autocrine signaling circuit in hepatic stellate cells underlies advanced fibrosis in nonalcoholic steatohepatitis
Wang S, Li K, Pickholz E, Dobie R, Matchett K, Henderson N, Carrico C, Driver I, Borch Jensen M, Chen L, Petitjean M, Bhattacharya D, Fiel M, Liu X, Kisseleva T, Alon U, Adler M, Medzhitov R, Friedman S. An autocrine signaling circuit in hepatic stellate cells underlies advanced fibrosis in nonalcoholic steatohepatitis. Science Translational Medicine 2023, 15: eadd3949. PMID: 36599008, PMCID: PMC10686705, DOI: 10.1126/scitranslmed.add3949.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsAdvanced hepatic fibrosisNonalcoholic steatohepatitisAdvanced fibrosisHepatic fibrosisHSC activationStellate cellsMurine nonalcoholic steatohepatitisStage-specific therapyHuman nonalcoholic steatohepatitisHuman HSC activationNeurotrophic receptor tyrosine kinaseDrug targetsSingle-nucleus RNA sequencingAdvanced diseaseAntifibrotic efficacyAntifibrotic therapyFibrosisTherapeutic paradigmAutocrine interactionsPharmacological inhibitionReceptor tyrosine kinasesSteatohepatitisStrongest predictorTherapy
2021
Microenvironment controls inflammatory response in macrophages
Zhou X, Pope S, Medzhitov R. Microenvironment controls inflammatory response in macrophages. The Journal Of Immunology 2021, 206: 111.03-111.03. DOI: 10.4049/jimmunol.206.supp.111.03.Peer-Reviewed Original ResearchInflammatory gene expressionInflammatory responseInflammatory response to lipopolysaccharideGene expressionModulate immune functionResponse to lipopolysaccharideControlling inflammatory gene expressionControlling inflammatory responsesTissue environmentPH-sensing receptorImmune cellsInflammatory conditionsInflammatory programGene-specific mannerTissue dysfunctionImmune functionNF-kBTissue microenvironmentPathway activationNarrow homeostatic rangeChromatin landscapeGene classesTissue homeostasisTranscriptional circuitsChromatin remodeling
2020
Longitudinal analyses reveal immunological misfiring in severe COVID-19
Lucas C, Wong P, Klein J, Castro TBR, Silva J, Sundaram M, Ellingson MK, Mao T, Oh JE, Israelow B, Takahashi T, Tokuyama M, Lu P, Venkataraman A, Park A, Mohanty S, Wang H, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Muenker MC, Fournier JB, Campbell M, Odio CD, Casanovas-Massana A, Herbst R, Shaw A, Medzhitov R, Schulz W, Grubaugh N, Dela Cruz C, Farhadian S, Ko A, Omer S, Iwasaki A. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020, 584: 463-469. PMID: 32717743, PMCID: PMC7477538, DOI: 10.1038/s41586-020-2588-y.Peer-Reviewed Original ResearchConceptsSevere COVID-19Moderate COVID-19Immune signaturesDisease outcomeCOVID-19Disease trajectoriesInterleukin-5Early immune signaturesInnate cell lineagesType 2 effectorsT cell numbersPoor clinical outcomeWorse disease outcomesImmune response profileCoronavirus disease 2019Distinct disease trajectoriesCytokine levelsImmunological correlatesImmune profileClinical outcomesEarly elevationImmune profilingIL-13Immunoglobulin EDisease 2019
2014
Signaling through the Adaptor Molecule MyD88 in CD4+ T Cells Is Required to Overcome Suppression by Regulatory T Cells
Schenten D, Nish S, Yu S, Yan X, Lee H, Brodsky I, Pasman L, Yordy B, Wunderlich F, BrĂĽning J, Zhao H, Medzhitov R. Signaling through the Adaptor Molecule MyD88 in CD4+ T Cells Is Required to Overcome Suppression by Regulatory T Cells. Immunity 2014, 40: 814. DOI: 10.1016/j.immuni.2014.04.012.Peer-Reviewed Original Research
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