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 ligandsTemporal arteritis presenting as third nerve palsy - a case report and review of literature
Arya PV A, Madathanapalli K, Tenezaca F, Wang A. Temporal arteritis presenting as third nerve palsy - a case report and review of literature. Rheumatology International 2024, 44: 2245-2251. PMID: 38739224, DOI: 10.1007/s00296-024-05604-6.Peer-Reviewed Original ResearchGiant cell arteritisThird nerve palsyPupil-sparing third nerve palsyNerve palsyTemporal arteritisHistory of well-controlled hypertensionPresentation of giant cell arteritisDiagnosis of giant cell arteritisOral steroid taperPulse-dose steroidsWell-controlled hypertensionYear smoking historyLumbar spine stenosisLarge vessel vasculitisMonths follow-upSteroid taperJaw claudicationElevated ESRAcute abnormalitiesMicrovascular ischemiaPrimary presentationVessel vasculitisBladder cancerCase reportClinical manifestationsSmall-molecule CBP/p300 histone acetyltransferase inhibition mobilizes leukocytes from the bone marrow via the endocrine stress response
Jaschke N, Breining D, Hofmann M, Pählig S, Baschant U, Oertel R, Traikov S, Grinenko T, Saettini F, Biondi A, Stylianou M, Bringmann H, Zhang C, Yoshida T, Weidner H, Poller W, Swirski F, Göbel A, Hofbauer L, Rauner M, Scheiermann C, Wang A, Rachner T. Small-molecule CBP/p300 histone acetyltransferase inhibition mobilizes leukocytes from the bone marrow via the endocrine stress response. Immunity 2024, 57: 364-378.e9. PMID: 38301651, PMCID: PMC10923082, DOI: 10.1016/j.immuni.2024.01.005.Peer-Reviewed Original ResearchConceptsCorticotropin-releasing hormone receptor 1Hypothalamus-pituitary-adrenal glandAdrenocorticotropic hormoneBone marrowGranulocyte colony-stimulating factorAugmented host defenseMobilization of leukocytesColony-stimulating factorHistone acetyltransferase inhibitionHormone receptor 1Leukemic transformationG-CSFNeutrophil mobilizationReceptor 1Leukocyte mobilizationLeukocyte distributionHistone acetyltransferaseLeukocyte compartmentNeuroendocrine loopHost defenseEndocrine stress responseLeukocytesMarrowBloodReversible inhibition
2023
The neurocircuitry of fasting-induced glucocorticoid release
Jaschke N, Wang A. The neurocircuitry of fasting-induced glucocorticoid release. Cell Metabolism 2023, 35: 1497-1499. PMID: 37673035, DOI: 10.1016/j.cmet.2023.08.004.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 backgroundMature B cells and mesenchymal stem cells control emergency myelopoiesis
Lim V, Feng X, Miao R, Zehentmeier S, Ewing-Crystal N, Lee M, Tumanov A, Oh J, Iwasaki A, Wang A, Choi J, Pereira J. Mature B cells and mesenchymal stem cells control emergency myelopoiesis. Life Science Alliance 2023, 6: e202301924. PMID: 36717247, PMCID: PMC9889502, DOI: 10.26508/lsa.202301924.Peer-Reviewed Original ResearchConceptsMarrow mesenchymal stem cellsSystemic inflammationMature B cellsB cellsEmergency myelopoiesisMesenchymal stem cellsIL-1 receptorBone marrow mesenchymal stem cellsStem cellsMyeloid cell productionMonocyte numbersB lineage cellsCCL2 productionViral infectionLymphotoxin α1β2InflammationReduced survivalLymphopoietic activityMyelopoiesisLymphopoiesisImportant regulatorLTβRCell productionCellsGenetic blocking
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 studiesInflammationCellsThe matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging
Ryu S, Sidorov S, Ravussin E, Artyomov M, Iwasaki A, Wang A, Dixit VD. The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging. Immunity 2022, 55: 1609-1626.e7. PMID: 35963236, PMCID: PMC9474643, DOI: 10.1016/j.immuni.2022.07.007.Peer-Reviewed Original ResearchConceptsToll-like receptor 4ISG inductionMatricellular proteinPro-inflammatory phenotypeAnti-inflammatory macrophagesInterferon-stimulated gene expressionAdipocyte-specific deletionInhibition of glycolysisImmunometabolic adaptationsMyD88 pathwayReceptor 4Chronic diseasesFunctional declineCaloric restrictionInterferon responseHealth spanMacrophagesInflammationMitochondrial respirationSPARCInductionGene expressionAdipokinesObesityIFN
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
051 Non-steroidal anti-inflammatory drugs act as adjuvant in allergic sensitization
Eisenstein A, Hilliard B, Wang A. 051 Non-steroidal anti-inflammatory drugs act as adjuvant in allergic sensitization. Journal Of Investigative Dermatology 2020, 140: s5. DOI: 10.1016/j.jid.2020.03.053.Peer-Reviewed Original ResearchOrigin 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 signalsHyperglycemiaInflammationCytokinesMortalityHormoneLess Pain, More Gain: Should Placebo Be a Clinical Therapeutic?
Uchendu SN, Wang A. Less Pain, More Gain: Should Placebo Be a Clinical Therapeutic? Arthritis & Rheumatology 2020, 72: 511-514. PMID: 31729836, DOI: 10.1002/art.41168.Peer-Reviewed Original Research
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 temperatureInfectionMetabolismSepsisInflammationAdministrationHormoneNot the usual suspect: type I interferon–responsive T cells drive infection-induced cachexia
Wang A, Medzhitov R. Not the usual suspect: type I interferon–responsive T cells drive infection-induced cachexia. Nature Immunology 2019, 20: 666-667. PMID: 31110313, DOI: 10.1038/s41590-019-0374-5.Peer-Reviewed Original ResearchCounting Calories: The Cost of Inflammation
Wang A, Medzhitov R. Counting Calories: The Cost of Inflammation. Cell 2019, 177: 223-224. PMID: 30951664, DOI: 10.1016/j.cell.2019.03.022.Peer-Reviewed Original ResearchSpecific 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
The expression of CXCR4/CXCL12 determines subsets of patients in systemic lupus erythematosus
Guilpain P, Wang A, Chong B, Chouzenoux S, Guillevin L, Zhou X, Lin F, Fairhurst A, Boudreaux C, Roux C, Wakeland E, Davis L, Batteux F, Mohan C. The expression of CXCR4/CXCL12 determines subsets of patients in systemic lupus erythematosus. Journal Of Translational Medicine 2011, 9: p60. PMCID: PMC3242291, DOI: 10.1186/1479-5876-9-s2-p60.Peer-Reviewed Original Research