2024
KLF13 promotes SLE pathogenesis by modifying chromatin accessibility of key proinflammatory cytokine genes
Wang A, Fairhurst A, Liu K, Wakeland B, Barnes S, Malladi V, Viswanathan K, Arana C, Dozmorov I, Singhar A, Du Y, Imam M, Moses A, Chen C, Sunkavalli A, Casco J, Rakheja D, Li Q, Mohan C, Clayberger C, Wakeland E, Khan S. KLF13 promotes SLE pathogenesis by modifying chromatin accessibility of key proinflammatory cytokine genes. Communications Biology 2024, 7: 1446. PMID: 39506084, PMCID: PMC11541912, DOI: 10.1038/s42003-024-07099-0.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusMyeloid cellsLupus nephritisT cellsKidneys of lupus-prone miceSystemic lupus erythematosus pathogenesisLevels of proinflammatory cytokinesLupus-prone miceActivated myeloid cellsActivated T cellsT cell activationProduction of RANTEST cell hyperactivityProinflammatory cytokine genesAssociated with increased productionLupus pathogenesisProinflammatory cytokines/chemokinesSle1 locusLupus erythematosusImmune activationProinflammatory cytokinesCytokine signaling pathwaysCytokine genesGenome-wide transcriptional changesReceptor ligands
2023
Immune 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 background
2022
Dickkopf1 fuels inflammatory cytokine responses
Jaschke N, Pählig S, Sinha A, Adolph T, Colunga M, Hofmann M, Wang A, Thiele S, Schwärzler J, Kleymann A, Gentzel M, Tilg H, Wielockx B, Hofbauer L, Rauner M, Göbel A, Rachner T. Dickkopf1 fuels inflammatory cytokine responses. Communications Biology 2022, 5: 1391. PMID: 36539532, PMCID: PMC9765382, DOI: 10.1038/s42003-022-04368-8.Peer-Reviewed Original ResearchConceptsInflammatory cytokine responseCytokine responsesCell-autonomous functionCell-autonomous mechanismsElevated cytokine productionMolecular underpinningsNon-malignant cellsCytokine receptorsHuman diseasesPharmacological neutralizationInflammatory toneInflammatory componentCytokine productionCancer cellsGenetic deletionInflammatory responseRelA activityDKK1Mouse modelDisease trajectoriesHealthy populationCell modelAdditional studiesInflammationCells
2021
Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice
Ryu S, Shchukina I, Youm YH, Qing H, Hilliard B, Dlugos T, Zhang X, Yasumoto Y, Booth CJ, Fernández-Hernando C, Suárez Y, Khanna K, Horvath TL, Dietrich MO, Artyomov M, Wang A, Dixit VD. Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice. ELife 2021, 10: e66522. PMID: 34151773, PMCID: PMC8245129, DOI: 10.7554/elife.66522.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietCoronavirus infectionAged miceT cellsHigher systemic inflammationInfected aged miceCOVID-19 severityCOVID-19 infectionActivation of ketogenesisMouse hepatitis virus strain A59Systemic inflammationInflammatory damageInfluenza infectionClinical hallmarkNLRP3 inflammasomeImmune surveillanceAdipose tissuePotential treatmentInfectionMiceStrongest predictorLungMortalityAge
2020
Origin and Function of Stress-Induced IL-6 in Murine Models
Qing H, Desrouleaux R, Israni-Winger K, Mineur YS, Fogelman N, Zhang C, Rashed S, Palm NW, Sinha R, Picciotto MR, Perry RJ, Wang A. Origin and Function of Stress-Induced IL-6 in Murine Models. Cell 2020, 182: 372-387.e14. PMID: 32610084, PMCID: PMC7384974, DOI: 10.1016/j.cell.2020.05.054.Peer-Reviewed Original ResearchMeSH KeywordsAdipose Tissue, BrownAnimalsBone Marrow CellsBone Marrow TransplantationBrainChemokinesCytokinesDisease Models, AnimalGluconeogenesisHyperglycemiaInterleukin-6LiverMaleMiceMice, Inbred C57BLMice, KnockoutReceptors, Adrenergic, beta-3Receptors, Interleukin-6Stress, PsychologicalUncoupling Protein 1ConceptsInterleukin-6Subsequent inflammatory challengeAcute psychological stressBrown adipose tissueDominant cytokineImmunometabolic reprogrammingInflammatory challengeEndocrine organMurine modelMouse modelAdipose tissueNeuropsychiatric diseasesAcute stressHepatic gluconeogenesisStress hormonesBrown adipocytesPsychological stressDependent fashionDiseaseInstructive signalsHyperglycemiaInflammationCytokinesMortalityHormone
2019
GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance
Luan HH, Wang A, Hilliard B, Carvalho F, Rosen CE, Ahasic A, Herzog E, Kang I, Pisani MA, Yu S, Zhang C, Ring A, Young L, Medzhitov R. GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance. Cell 2019, 178: 1231-1244.e11. PMID: 31402172, PMCID: PMC6863354, DOI: 10.1016/j.cell.2019.07.033.Peer-Reviewed Original ResearchConceptsViral infectionTriglyceride metabolismImpaired cardiac functionRole of GDF15Differentiation factor 15Plasma triglyceride levelsSympathetic outflowInflammatory damageTriglyceride levelsCardiac functionInflammatory responseExogenous administrationProtective effectFactor 15GDF15Central mediatorTissue toleranceBody temperatureInfectionMetabolismSepsisInflammationAdministrationHormoneSpecific sequences of infectious challenge lead to secondary hemophagocytic lymphohistiocytosis-like disease in mice
Wang A, Pope SD, Weinstein JS, Yu S, Zhang C, Booth CJ, Medzhitov R. Specific sequences of infectious challenge lead to secondary hemophagocytic lymphohistiocytosis-like disease in mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 2200-2209. PMID: 30674681, PMCID: PMC6369774, DOI: 10.1073/pnas.1820704116.Peer-Reviewed Original ResearchConceptsSecondary hemophagocytic lymphohistiocytosisAssociated transcriptional programRNA sequencing analysisBone marrow-derived macrophagesTranscriptional programsTranscriptional profilingMarrow-derived macrophagesBone marrow macrophagesTranscriptional profilesNonlethal doseMitochondrial functionToll-like receptor agonistsSequencing analysisSpecific sequencesSetting of infectionGlycolytic metabolismMarrow macrophagesUseful therapeutic strategyGlycolysis inhibitorLethal stateHyperinflammatory stateHyperinflammatory responseOxidative metabolismHemophagocytic lymphohistiocytosisMortal complicationsAn evolutionary perspective on immunometabolism
Wang A, Luan HH, Medzhitov R. An evolutionary perspective on immunometabolism. Science 2019, 363 PMID: 30630899, PMCID: PMC6892590, DOI: 10.1126/science.aar3932.Peer-Reviewed Original ResearchConceptsMetabolic programsBiological functionsCell fate decisionsLife history theoryDifferent biological functionsDistinct metabolic programsOrganismal physiologyFate decisionsField of immunometabolismAnabolic metabolismCell quiescenceBiological processesHistory theoryEvolutionary perspectiveEcological principlesCatabolic metabolismDe novoBiological infrastructureMetabolismImmunometabolismRecent studiesDifferentiationPhysiologyNovoNutrients
2018
Glucose metabolism mediates disease tolerance in cerebral malaria
Wang A, Huen SC, Luan HH, Baker K, Rinder H, Booth CJ, Medzhitov R. Glucose metabolism mediates disease tolerance in cerebral malaria. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 11042-11047. PMID: 30291189, PMCID: PMC6205430, DOI: 10.1073/pnas.1806376115.Peer-Reviewed Original ResearchConceptsCerebral malariaGlucose metabolismBlood-brain barrier permeabilityAlternative fuel substrateCerebral malaria modelInflammation-induced anorexiaParasitic disease malariaVehicle-treated animalsAcute inflammatory conditionsTissue-protective mechanismsPotential therapeutic targetDifferent inflammatory statesInhibition of glycolysisViral inflammationANKA infectionThrombotic complicationsInfectious inflammationInflammatory stateBacterial inflammationImmune infiltrationInflammatory conditionsInflammatory diseasesMale miceBarrier permeabilitySickness behavior
2016
Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation
Wang A, Huen SC, Luan HH, Yu S, Zhang C, Gallezot JD, Booth CJ, Medzhitov R. Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation. Cell 2016, 166: 1512-1525.e12. PMID: 27610573, PMCID: PMC5555589, DOI: 10.1016/j.cell.2016.07.026.Peer-Reviewed Original ResearchConceptsNutritional supplementationMagnitude of inflammationRole of anorexiaViral inflammationViral sepsisStereotypic behavioral responsesAcute infectionBacterial sepsisInfluenza infectionInflammatory stateSickness behaviorViral infectionFamiliar symptomsGlucose utilizationHost defenseAnorexiaInfectionViral modelSepsisTissue toleranceInflammationSocial withdrawalSupplementationMetabolic requirementsPathogen load
2011
Use of mouse hematopoietic stem and progenitor cells to treat acute kidney injury
Li L, Black R, Ma Z, Yang Q, Wang A, Lin F. Use of mouse hematopoietic stem and progenitor cells to treat acute kidney injury. American Journal Of Physiology. Renal Physiology 2011, 302: f9-f19. PMID: 21937606, PMCID: PMC3251347, DOI: 10.1152/ajprenal.00377.2011.Peer-Reviewed Original ResearchConceptsAcute kidney injuryKidney injuryMouse hematopoietic stemProgenitor cellsHematopoietic stemEpithelial marker E-cadherinRenal ischemic injuryTubular cell deathCell fate conversionMarker E-cadherinEmbryonic kidney organ cultureHistone deacetylase inhibitorsKidney organ culturesIschemic injuryKidney functionPostischemic kidneyTubular repairRenal capsuleRenal repairRenotrophic factorIGF-1Intravenous injectionEffective treatmentFate conversionEpithelial proliferation
2009
CXCR4/CXCL12 Hyperexpression Plays a Pivotal Role in the Pathogenesis of Lupus
Wang A, Fairhurst AM, Tus K, Subramanian S, Liu Y, Lin F, Igarashi P, Zhou XJ, Batteux F, Wong D, Wakeland EK, Mohan C. CXCR4/CXCL12 Hyperexpression Plays a Pivotal Role in the Pathogenesis of Lupus. The Journal Of Immunology 2009, 182: 4448-4458. PMID: 19299746, PMCID: PMC2946082, DOI: 10.4049/jimmunol.0801920.Peer-Reviewed Original ResearchConceptsMurine modelIncreased CXCR4 expressionPathogenesis of lupusB cell subsetsPromising therapeutic targetCXCR4/CXCL12Multiple murine modelsB cell survivalLupus nephritisActive nephritisSerum autoantibodiesCell subsetsCXCR4 expressionInflammatory cytokinesNephritic kidneysOrgan diseasePathogenic rolePlasma cellsLeukocyte traffickingTherapeutic targetLupusPeptide antagonistCXCR4Surface moleculesNephritis