2024
Small-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
Mature 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
Less 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 ResearchAn 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
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
2010
Dysregulated expression of CXCR4/CXCL12 in subsets of patients with systemic lupus erythematosus
Wang A, Guilpain P, Chong BF, Chouzenoux S, Guillevin L, Du Y, Zhou XJ, Lin F, Fairhurst A, Boudreaux C, Roux C, Wakeland EK, Davis LS, Batteux F, Mohan C. Dysregulated expression of CXCR4/CXCL12 in subsets of patients with systemic lupus erythematosus. Arthritis & Rheumatism 2010, 62: 3436-3446. PMID: 20722038, PMCID: PMC8972909, DOI: 10.1002/art.27685.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusLupus nephritisSLE patientsCXCR4 expressionPeripheral blood leukocytesNeuropsychiatric SLEB cellsLupus erythematosusBlood leukocytesSLE Disease Activity Index (SLEDAI) scoreClasses of LNDisease activity index scoreSeverity of LNNeuropsychiatric systemic lupus erythematosusCentral nervous system involvementClass IV lupus nephritisActive neuropsychiatric systemic lupus erythematosusCXCR4/CXCL12 axisAnti-CXCL12 antibodyActivity index scoreNervous system involvementSubset of patientsMurine lupus modelsGlomeruli of kidneysPotential therapeutic target