2024
Gut microbiota from B-cell-specific TLR9-deficient NOD mice promote IL-10+ Breg cells and protect against T1D
Yang X, Huang J, Peng J, Wang P, Wong F, Wang R, Wang D, Wen L. Gut microbiota from B-cell-specific TLR9-deficient NOD mice promote IL-10+ Breg cells and protect against T1D. Frontiers In Immunology 2024, 15: 1413177. PMID: 38903498, PMCID: PMC11187306, DOI: 10.3389/fimmu.2024.1413177.Peer-Reviewed Original ResearchGut microbiotaGerm-free miceToll-like receptor 9Increased gut permeabilityIntestinal microbiotaGut permeabilityT1D developmentGut microbiota compositionFecal samplesTransferred to germ-free miceGut barrier integrityBreg cell differentiationMicrobiota influenceMucin degradationMicrobiota compositionBreg cellsAltered microbiotaMicrobiota impactMicrobiotaGene expressionImmune regulationDevelopment of T1DCell differentiationGutNOD miceTlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis
Wang P, Yang X, Zhang L, Sha S, Huang J, Peng J, Gu J, Pearson J, Hu Y, Zhao H, Wong F, Wang Q, Wen L. Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis. Nature Communications 2024, 15: 4232. PMID: 38762479, PMCID: PMC11102548, DOI: 10.1038/s41467-024-48611-8.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Gut microbiotaGut microbial communityTransferred to germ-free miceB cellsGerm-free miceTLR9 deficiencyKO miceGene sequencesGerminal center B cellsMicrobial communitiesMarginal zone B cellsGut dysbiosisFollicular helper cellsSelf-DNAMetabolic homeostasisAssociated with increased frequencyPro-inflammatory stateFat tissue inflammationGutHigh-fat dietMicrobiotaHelper cellsT cellsControl miceEffects of gut microbiome on type 1 diabetes susceptibility and complications: A large‐scale bidirectional Mendelian randomization and external validation study
Guo K, Ye J, Li J, Huang J, Zhou Z. Effects of gut microbiome on type 1 diabetes susceptibility and complications: A large‐scale bidirectional Mendelian randomization and external validation study. Diabetes Obesity And Metabolism 2024, 26: 3306-3317. PMID: 38751358, DOI: 10.1111/dom.15658.Peer-Reviewed Original ResearchHigh-density lipoproteinOphthalmic complicationsT1D complicationsComplications of type 1 diabetesType 1 diabetes susceptibilityData of patientsRisk of T1DSmall high-density lipoproteinGut microbiomeComplications of T1DType 1 diabetesEffect of gut microbiomeExternal validation studyEffects of gut microbiotaCirculating metabolitesMultivariable MR analysisHealthy controlsComplicationsMR analysisMendelian randomizationRelative abundanceEubacterium coprostanoligenes groupMetabolic diseasesT1DPatientsGut microbiota and therapy for obesity and type 2 diabetes
Zhang L, Wang P, Huang J, Xing Y, Wong F, Suo J, Wen L. Gut microbiota and therapy for obesity and type 2 diabetes. Frontiers In Endocrinology 2024, 15: 1333778. PMID: 38596222, PMCID: PMC11002083, DOI: 10.3389/fendo.2024.1333778.Peer-Reviewed Original ResearchGut microbiota compositionGut microbiotaMicrobiota compositionType 2 diabetesFunction of gut microbiotaHomeostasis of gut microbiotaMicrobiota-based approachesModulating gut microbiotaBariatric surgeryEffective anti-obesity treatmentQuality of life of individualsMicrobiotaMildly obese patientsSustained weight lossAssociated with obesityDiminished quality of lifeAnti-obesity treatmentObesity management strategiesGutQuality of lifeNon-surgical interventionsIncreased medical costsPublic health crisisMusculoskeletal disordersObese patients
2023
Adverse effects of gestational diabetes mellitus on fetal monocytes revealed by single-cell RNA sequencing
Yin M, Zhang Y, Li X, Liu S, Huang J, Yu H, Li X. Adverse effects of gestational diabetes mellitus on fetal monocytes revealed by single-cell RNA sequencing. IScience 2023, 27: 108637. PMID: 38188508, PMCID: PMC10770529, DOI: 10.1016/j.isci.2023.108637.Peer-Reviewed Original ResearchGestational diabetes mellitusCord blood mononuclear cellsBlood mononuclear cellsGDM mothersDiabetes mellitusMononuclear cellsCord bloodFetal monocytesMyeloid cellsMaternal gestational diabetes mellitusPeripheral blood mononuclear cellsAtherosclerotic cardiovascular diseasePrevalent metabolic disorderLong-term riskProliferation-related pathwaysCardiovascular diseaseMetabolic disordersNeutrophil granulocytesMetabolic diseasesSingle-cell RNA sequencingMonocytesPhagocytic abilityAdverse effectsPotential mechanismsMellitusElevated glucose metabolism driving pro-inflammatory response in B cells contributes to the progression of type 1 diabetes
Li Z, Zhao M, Li J, Luo W, Huang J, Huang G, Xie Z, Xiao Y, Huang J, Li X, Zhao B, Zhou Z. Elevated glucose metabolism driving pro-inflammatory response in B cells contributes to the progression of type 1 diabetes. Clinical Immunology 2023, 255: 109729. PMID: 37562723, DOI: 10.1016/j.clim.2023.109729.Peer-Reviewed Original ResearchConceptsType 1 diabetesPro-inflammatory responseB cellsGlucose metabolismCytokine productionAberrant B cell responsesNon-obese diabetic (NOD) micePro-inflammatory cytokine productionHigh blood glucose levelsOnset of diabetesInflammatory cytokine productionAdaptive immune responsesB cell responsesCross-sectional cohortImmune system failureDiabetic mouse modelB cell functionBlood glucose levelsB cell populationsB cell metabolismPancreatic beta cellsB cell proliferationElevated glucose metabolismInsulitis developmentNOD miceDistinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study
Hu J, Ding J, Li X, Li J, Zheng T, Xie L, Li C, Tang Y, Guo K, Huang J, Liu S, Yan J, Peng W, Hou C, Wen L, Xu A, Zhou Z, Xiao Y. Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study. EClinicalMedicine 2023, 62: 102132. PMID: 37593224, PMCID: PMC10430172, DOI: 10.1016/j.eclinm.2023.102132.Peer-Reviewed Original ResearchAdult-onset T1DHealthy controlsGut microbiotaT1D patientsShort-chain fatty acid-producing bacteriaPopulation-based cross-sectional studyGut microbial alterationsRecent epidemiological dataType 1 diabetesCross-sectional studyT2D patientsIntestinal disturbancesDifferential diagnosisSerum metabolitesEpidemiological dataPatientsStudy subjectsT1DDiabetesSignificant differencesAcid-producing bacteriaMicrobiotaMicrobial profilesNational Key ResearchMicrobial alterationsEmerging trends and focus on the link between gut microbiota and type 1 diabetes: A bibliometric and visualization analysis
Guo K, Li J, Li X, Huang J, Zhou Z. Emerging trends and focus on the link between gut microbiota and type 1 diabetes: A bibliometric and visualization analysis. Frontiers In Microbiology 2023, 14: 1137595. PMID: 36970681, PMCID: PMC10033956, DOI: 10.3389/fmicb.2023.1137595.Peer-Reviewed Original ResearchNLRP6 deficiency expands a novel CD103+ B cell population that confers immune tolerance in NOD mice
Pearson J, Peng J, Huang J, Yu X, Tai N, Hu Y, Sha S, Flavell R, Zhao H, Wong F, Wen L. NLRP6 deficiency expands a novel CD103+ B cell population that confers immune tolerance in NOD mice. Frontiers In Immunology 2023, 14: 1147925. PMID: 36911699, PMCID: PMC9995752, DOI: 10.3389/fimmu.2023.1147925.Peer-Reviewed Original ResearchConceptsNlrp6-deficient miceType 1 diabetesNLRP6 deficiencyB cellsIL-10Non-obese diabetic (NOD) miceType 1 diabetes developmentRole of NLRP6Germ-free miceT cell proliferationB cell populationsIntestinal epithelial cellsBreg populationAutoimmune diabetesNOD miceCrohn's diseaseImmune toleranceDiabetes developmentDiabetic miceImmune cellsCD103Inflammasome proteinsImmune responseNLRP6Gut microbiota
2022
Identification of monocyte-related transcriptomic signature of peripheral blood mononuclear cells in type 1 diabetes
Yin M, Zhang Y, Huang J, Li X, Yu H, Li X. Identification of monocyte-related transcriptomic signature of peripheral blood mononuclear cells in type 1 diabetes. Chinese Medical Journal 2022, 135: 2608-2610. PMID: 36583923, PMCID: PMC9943828, DOI: 10.1097/cm9.0000000000002142.Peer-Reviewed Original ResearchGene Expression Signatures Reveal Common Virus Infection Pathways in Target Tissues of Type 1 Diabetes, Hashimoto’s Thyroiditis, and Celiac Disease
Yin M, Zhang Y, Liu S, Huang J, Li X. Gene Expression Signatures Reveal Common Virus Infection Pathways in Target Tissues of Type 1 Diabetes, Hashimoto’s Thyroiditis, and Celiac Disease. Frontiers In Immunology 2022, 13: 891698. PMID: 35795668, PMCID: PMC9251511, DOI: 10.3389/fimmu.2022.891698.Peer-Reviewed Original ResearchConceptsHashimoto's thyroiditisCeliac diseaseAutoimmune diseasesTarget tissuesAutoimmune disordersHuman T-lymphotropic virus type 1Type 1 diabetes patientsMore autoimmune disordersPathogenesis of T1DType 1 diabetesCommon gene expression changesVirus type 1Gene expression signaturesSimplex infectionVirus infection pathwaysDiabetes patientsInfluenza APositive individualsVirus infectionT1DThyroiditisImmune systemType 1Gene signatureSimilar molecular signaturesHost gene effects on gut microbiota in type 1 diabetes
Guo K, Huang J, Zhou Z. Host gene effects on gut microbiota in type 1 diabetes. Biochemical Society Transactions 2022, 50: 1133-1142. PMID: 35521897, PMCID: PMC9246325, DOI: 10.1042/bst20220004.Peer-Reviewed Original ResearchConceptsType 1 diabetesMicrobiome compositionPancreatic β-cell lossT1D susceptibility genesT1D developmentHost genesImmunity genesGenetic lociGut microbiotaGene effectsModel of T1DNon-obese diabetic (NOD) miceOrgan-specific autoimmune diseasesΒ-cell lossGenesSusceptibility genesGenetic backgroundGenetic variantsMicrobiota interactionsRisk of T1DPancreatic islet autoantigensGut microbiota diversityGut microbiome compositionIslet autoimmunityT1D progression
2021
IL-10 Deficiency Accelerates Type 1 Diabetes Development via Modulation of Innate and Adaptive Immune Cells and Gut Microbiota in BDC2.5 NOD Mice
Huang J, Tan Q, Tai N, Pearson JA, Li Y, Chao C, Zhang L, Peng J, Xing Y, Zhang L, Hu Y, Zhou Z, Wong FS, Wen L. IL-10 Deficiency Accelerates Type 1 Diabetes Development via Modulation of Innate and Adaptive Immune Cells and Gut Microbiota in BDC2.5 NOD Mice. Frontiers In Immunology 2021, 12: 702955. PMID: 34394099, PMCID: PMC8362616, DOI: 10.3389/fimmu.2021.702955.Peer-Reviewed Original ResearchConceptsNOD miceProportion of neutrophilsT cellsGut microbiotaDiabetes developmentT cell-mediated destructionT cell receptor transgenicType 1 diabetes developmentAccelerated diabetes developmentInhibition of diabetesModulation of InnatePathogenicity of CD4Cell-mediated destructionAdaptive immune cellsObese diabetic miceT regulatory (Treg) cellsDevelopment of diabetesPrevention of diabetesActivation of CD4Modulation of neutrophilsType 1 diabetesGut microbiota compositionInsulin-producing β-cellsSevere insulitisSpontaneous diabetesInnate immunity in latent autoimmune diabetes in adults
Huang J, Pearson JA, Wong FS, Wen L, Zhou Z. Innate immunity in latent autoimmune diabetes in adults. Diabetes/Metabolism Research And Reviews 2021, 38: e3480. PMID: 34156143, PMCID: PMC8813511, DOI: 10.1002/dmrr.3480.Peer-Reviewed Original ResearchConceptsType 1 diabetesDendritic cellsImmune cellsT cellsInnate immunityPathogenesis of LADALatent autoimmune diabetesAdaptive immune cellsPancreas of patientsType 2 diabetesImmune-associated genesIslet β-cellsAutoimmune diabetesClinical featuresImmunological reasonsAutoimmune diseasesRat modelB cellsDiabetesΒ-cellsImmunityPotential rolePathogenesisLADADiseaseToll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function
Huang J, Peng J, Pearson JA, Efthimiou G, Hu Y, Tai N, Xing Y, Zhang L, Gu J, Jiang J, Zhao H, Zhou Z, Wong FS, Wen L. Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function. Cellular & Molecular Immunology 2021, 18: 328-338. PMID: 33432061, PMCID: PMC8027372, DOI: 10.1038/s41423-020-00590-8.Peer-Reviewed Original ResearchConceptsType 1 diabetes developmentToll-like receptorsType 1 diabetesDiabetes developmentB cellsTLR7 deficiencyNOD miceB cell differentiationT cellsClassical MHC class I moleculesHuman type 1 diabetesImmunodeficient NOD miceNOD B cellsDiabetogenic T cellsAntigen-presenting functionNonobese diabetic (NOD) miceT cell responsesB cell functionMHC class I moleculesPattern recognition receptorsT cell activationPathogen molecular patternsClass I moleculesDiabetogenic CD4Cytotoxic CD8
2020
Abnormal Neutrophil Transcriptional Signature May Predict Newly Diagnosed Latent Autoimmune Diabetes in Adults of South China
Xing Y, Lin Q, Tong Y, Zhou W, Huang J, Wang Y, Huang G, Li Y, Xiang Z, Zhou Z, Li T, Xiao Y. Abnormal Neutrophil Transcriptional Signature May Predict Newly Diagnosed Latent Autoimmune Diabetes in Adults of South China. Frontiers In Endocrinology 2020, 11: 581902. PMID: 33391182, PMCID: PMC7775642, DOI: 10.3389/fendo.2020.581902.Peer-Reviewed Original ResearchConceptsSex-matched healthy controlsLADA patientsHealthy controlsDevelopment of LADAPathological processesPeripheral blood neutrophilsCytokine-cytokine receptor interactionReal-time polymerase chain reactionLatent AutoimmuneAdhesion molecule signalingAutoimmune diabetesFunction deteriorationNeutrophil numbersPeripheral neutrophilsBlood neutrophilsPolymerase chain reactionPathological alterationsCell differentiationLeukocyte degranulationMyeloid cell differentiationGenomes (KEGG) pathway enrichmentPatientsPresent study resultsNeutrophilsTranscriptional levelTLR9 Deficiency in B Cells Promotes Immune Tolerance via Interleukin-10 in a Type 1 Diabetes Mouse Model.
Sha S, Pearson JA, Peng J, Hu Y, Huang J, Xing Y, Zhang L, Zhu Y, Zhao H, Wong FS, Chen L, Wen L. TLR9 Deficiency in B Cells Promotes Immune Tolerance via Interleukin-10 in a Type 1 Diabetes Mouse Model. Diabetes 2020, 70: 504-515. PMID: 33154070, PMCID: PMC7881860, DOI: 10.2337/db20-0373.Peer-Reviewed Original ResearchConceptsToll-like receptor 9B cellsNOD miceInterleukin-10IL-10-producing B cellsType 1 diabetes developmentAdaptive immune stimuliΒ-cell autoimmunityB-cell-specific deficiencyNovel therapeutic strategiesInnate immune moleculesB cell-specific deletionT1D developmentDiabetes protectionIL-10TLR9 deficiencyImmune toleranceDiabetes developmentReceptor 9T1D treatmentTLR9 pathwayImmune stimuliMouse modelTherapeutic strategiesMetalloproteinase-1Altered Systemic and Intestinal IgA Immune Responses in Individuals With Type 1 Diabetes
Huang J, Huang G, Li X, Hu F, Xie Z, Xiao Y, Luo S, Chao C, Guo K, Wong FS, Zhou Z, Wen L. Altered Systemic and Intestinal IgA Immune Responses in Individuals With Type 1 Diabetes. The Journal Of Clinical Endocrinology & Metabolism 2020, 105: dgaa590. PMID: 32860693, PMCID: PMC7549925, DOI: 10.1210/clinem/dgaa590.Peer-Reviewed Original ResearchConceptsIgA-bound bacteriaType 1 diabetesHealthy control individualsIgA immune responseControl individualsIgA immunityAutoantibody titersIgA concentrationsImmune responseType 1 diabetes patientsΒ-cell autoimmunityLonger disease durationSerum IgA concentrationNovel therapeutic targetEnzyme-linked immunosorbentDisease durationIgA levelsDiabetes patientsDiabetes displayGut homeostasisBlood samplesOral cavityTherapeutic targetDiabetesHost immunityGut microbial metabolites alter IgA immunity in type 1 diabetes
Huang J, Pearson JA, Peng J, Hu Y, Sha S, Xing Y, Huang G, Li X, Hu F, Xie Z, Xiao Y, Luo S, Chao C, Wong F, Zhou Z, Wen L. Gut microbial metabolites alter IgA immunity in type 1 diabetes. JCI Insight 2020, 5 PMID: 32298241, PMCID: PMC7259536, DOI: 10.1172/jci.insight.135718.Peer-Reviewed Original ResearchConceptsType 1 diabetesGut microbiotaNOD miceImmune responseGerm-free NOD miceIgA immune responseIgA-mediated immunityHealthy control subjectsPotential therapeutic agentShort-chain fatty acid productionIgA immunityT1D preventionIgA responsesControl subjectsDecreased severityT1DTherapeutic agentsFunctional effectsMicrobiotaDiabetesPatientsUnderlying mechanismMiceImmunitySCFAAbnormal Peripheral Neutrophil Transcriptome in Newly Diagnosed Type 2 Diabetes Patients
Lin Q, Zhou W, Wang Y, Huang J, Hui X, Zhou Z, Xiao Y. Abnormal Peripheral Neutrophil Transcriptome in Newly Diagnosed Type 2 Diabetes Patients. Journal Of Diabetes Research 2020, 2020: 9519072. PMID: 32377527, PMCID: PMC7195634, DOI: 10.1155/2020/9519072.Peer-Reviewed Original ResearchConceptsType 2 diabetes patientsGene OntologyType 2 diabetesComprehensive transcriptome analysisKEGG pathway enrichment analysisCytokine receptor interaction pathwayMyeloid leukocyte activationPathway enrichment analysisReceptor interaction pathwayQPCR of genesGene expression analysisDiabetes patientsHealthy controlsUpregulated DEGsTranscriptome analysisTranscriptome levelGO analysisKEGG pathwaysRNA sequencingCell adhesion moleculeExpression analysisEnrichment analysisInteraction pathwayMolecular mechanismsDEGs