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
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 temperatureInfectionMetabolismSepsisInflammationAdministrationHormone
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