Lei Shen
Associate Research ScientistAbout
Research
Publications
2024
Sirtuin 6 inhibits group 3 innate lymphoid cell function and gut immunity by suppressing IL-22 production
Su X, Zhao L, Zhang H, Wang D, Sun J, Shen L. Sirtuin 6 inhibits group 3 innate lymphoid cell function and gut immunity by suppressing IL-22 production. Frontiers In Immunology 2024, 15: 1402834. PMID: 39253083, PMCID: PMC11381250, DOI: 10.3389/fimmu.2024.1402834.Peer-Reviewed Original ResearchCitrobacter rodentium infectionIL-22 productionSirtuin 6Regulating gut immune responsesNicotinamide adenine dinucleotide (NAD+)-dependent deacetylaseDextran sodium sulfate-induced colitis modelIntestinal epithelial cell differentiationGroup 3 innate lymphoid cellsDextran sodium sulfate-induced colitisEpithelial cell differentiationGut immune responseFlow cytometryEpigenetic regulationIncreased IL-22 productionCell-intrinsic mannerDependent deacetylaseIntestinal ILC3sCell numberIntestinal inflammatory responseLymphoid cell functionGut defenseConditional knockout miceGut immunityIL-22 expressionHost defenseSingle-cell analysis reveals a subpopulation of adipose progenitor cells that impairs glucose homeostasis
Wang H, Du Y, Huang S, Sun X, Ye Y, Sun H, Chu X, Shan X, Yuan Y, Shen L, Bi Y. Single-cell analysis reveals a subpopulation of adipose progenitor cells that impairs glucose homeostasis. Nature Communications 2024, 15: 4827. PMID: 38844451, PMCID: PMC11156882, DOI: 10.1038/s41467-024-48914-w.Peer-Reviewed Original ResearchConceptsAdipose progenitor cellsT2D patientsProgenitor cellsDiphtheria toxin A expressionHeterogeneous stromal cellsGlycemic disturbancesAdipose tissueInfluence of obesityGlucose homeostasisVisceral adipose tissueHuman visceral adipose tissueImpaired glucose homeostasisType 2 diabetesHunter-killer peptidesRegulating glucose homeostasisSingle-cell analysisAPC functionStromal cellsA expressionMetabolic homeostasisAdipocyte lipolysisT2D developmentPatientsT2DBioactive proteinsSUMO-specific protease 1 regulates germinal center B cell response through deSUMOylation of PAX5
Qi J, Yan L, Sun J, Huang C, Su B, Cheng J, Shen L. SUMO-specific protease 1 regulates germinal center B cell response through deSUMOylation of PAX5. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2314619121. PMID: 38776375, PMCID: PMC11145296, DOI: 10.1073/pnas.2314619121.Peer-Reviewed Original ResearchConceptsPaired box protein 5GC B cellsSUMO-specific protease 1Activation-induced cytidine deaminaseProtein SUMOylationClass switch recombinationProtein stabilityB cellsProtease 1B cell responsesProtein 5Cytidine deaminaseSENP1Up-regulatedGC B cell responsesSomatic hypermutationSUMOylationDeSUMOylationGerminal centersHigher affinityProduction of class-switched antibodiesGerminal center B cell responsesGC reactionMemory B cellsClass-switched antibodiesMetabolic regulator LKB1 controls adipose tissue ILC2 PD-1 expression and mitochondrial homeostasis to prevent insulin resistance
Sun J, Zhang Y, Zhang Q, Hu L, Zhao L, Wang H, Yuan Y, Niu H, Wang D, Zhang H, Liu J, Feng X, Su X, Qiu J, Sun J, Xu H, Zhang C, Wang K, Bi Y, Engleman E, Shen L. Metabolic regulator LKB1 controls adipose tissue ILC2 PD-1 expression and mitochondrial homeostasis to prevent insulin resistance. Immunity 2024, 57: 1289-1305.e9. PMID: 38772366, DOI: 10.1016/j.immuni.2024.04.024.Peer-Reviewed Original ResearchLiver kinase B1PD-1 expressionLKB1 deficiencyInsulin resistanceSuppressing Bcl-xL expressionBcl-xL expressionGroup 2 innate lymphoid cellsBlockade of PD-1Treatment of metabolic diseasesObesity-induced insulin resistanceFunction of ILC2sType 2 immunityMitochondrial homeostasisActivation of NFATObesity-associated insulin resistanceMitochondrial metabolismPrevent insulin resistanceKinase B1Exacerbate insulin resistanceEnhanced mitophagyMetabolic homeostasisILC2 responsesPD-1Genetic ablationLymphoid cellsLKB1 prevents ILC2 exhaustion to enhance antitumor immunity
Niu H, Zhang H, Wang D, Zhao L, Zhang Y, Zhou W, Zhang J, Su X, Sun J, Su B, Qiu J, Shen L. LKB1 prevents ILC2 exhaustion to enhance antitumor immunity. Cell Reports 2024, 43: 113579. PMID: 38670109, DOI: 10.1016/j.celrep.2023.113579.Peer-Reviewed Original ResearchAntitumor immunityPD-1Tumor immunityExpression of programmed cell death protein 1Group 2 innate lymphoid cellsBlockade of PD-1Cell death protein 1Lung melanoma metastasesAntitumor immune responseRegulating tumor immunityNuclear factor of activating T cells pathwayT-cell pathwayLiver kinase B1ILC2 functionMelanoma metastasesILC2sLymphoid cellsAllergic inflammationImmune homeostasisEffector functionsInactivating mutationsImmune responseHuman cancersCell pathwaysProtein 1Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage–tumor interaction axes among different lineages of pituitary neuroendocrine tumors
Lin S, Dai Y, Han C, Han T, Zhao L, Wu R, Liu J, Zhang B, Huang N, Liu Y, Lai S, Shi J, Wang Y, Lou M, Xie J, Cheng Y, Tang H, Yao H, Fang H, Zhang Y, Wu X, Shen L, Ye Y, Xue L, Wu Z. Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage–tumor interaction axes among different lineages of pituitary neuroendocrine tumors. Genome Medicine 2024, 16: 60. PMID: 38658971, PMCID: PMC11040908, DOI: 10.1186/s13073-024-01325-4.Peer-Reviewed Original ResearchConceptsTumor immune microenvironmentTumor-associated macrophagesTumor cell apoptosisTumor cellsImmune cellsNeuroendocrine tumorsQuantitative immunofluorescenceComposition of immune cellsInfiltration of immune cellsMultiplexed quantitative immunofluorescenceLevel of immune infiltrationScRNA-seqPituitary neuroendocrine tumorsCX3CR1+ macrophagesDiversity of tumorsCell apoptosisSignificance of macrophagesRNA sequencing samplesScRNA-seq dataCX3CR1+Subcutaneous xenograft experimentsImmune microenvironmentSingle-cell RNA sequencingImmunological environmentImmune infiltration
2023
Th1 bias of liver mucosal‐associated invariant T cells promotes hepatic gluconeogenesis in type 2 diabetes mellitus
Tang W, Ge K, Shen L, Wang H, Feng W, Sun X, Chu X, Zhu D, Yin H, Bi Y. Th1 bias of liver mucosal‐associated invariant T cells promotes hepatic gluconeogenesis in type 2 diabetes mellitus. Diabetes/Metabolism Research And Reviews 2023, 39: e3620. PMID: 36738300, DOI: 10.1002/dmrr.3620.Peer-Reviewed Original ResearchConceptsHepatic MAIT cellsMAIT cellsMAIT cell subsetsType 2 diabetes mellitusInnate-like T cell subsetMucosal-associated invariant T (MAIT) cellsHepatic gluconeogenesisMucosal-associated invariant T cellsExpression of pyruvate carboxylaseGene expression of pyruvate carboxylaseCell subsetsExpression of genesT2DM subjectsInvariant T cellsIFN-gMAIT cell frequencyPyruvate carboxylaseProduction of interleukin-17HepG2 cells co-culturedT cell subsetsTumor necrosis factor-aDevelopment of type 2 diabetes mellitusGene expressionDiagnosed T2DM subjectsMetabolic homoeostasis