2023
Elevated 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 ResearchMeSH KeywordsAnimalsCross-Sectional StudiesCytokinesDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1GlucoseHumansMiceMice, Inbred NODProto-Oncogene Proteins c-mycSignal TransductionConceptsType 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 miceNLRP6 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 ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 1Immune ToleranceInflammasomesInterleukin-10LipopolysaccharidesMiceMice, Inbred NODConceptsNlrp6-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 ResearchMeSH KeywordsAutoimmune DiseasesCeliac DiseaseDiabetes Mellitus, Type 1Hashimoto DiseaseHumansTranscriptomeVirus DiseasesConceptsHashimoto'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 ResearchMeSH KeywordsAnimalsAutoimmunityDiabetes Mellitus, Type 1Disease SusceptibilityGastrointestinal MicrobiomeInsulin-Secreting CellsMiceMice, Inbred NODConceptsType 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 ResearchMeSH KeywordsAdaptive ImmunityAnimalsDiabetes Mellitus, Type 1Gastrointestinal MicrobiomeImmunity, InnateInterleukin-10MiceMice, Inbred NODMice, KnockoutT-Lymphocytes, RegulatoryConceptsNOD 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 ResearchMeSH KeywordsAnimalsAutoantibodiesCD8-Positive T-LymphocytesDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2HumansImmunity, InnateLatent Autoimmune Diabetes in AdultsRatsConceptsType 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
TLR9 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 ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 1Disease Models, AnimalImmune ToleranceInsulin-Secreting CellsInterleukin-10MiceMice, Inbred NODSignal TransductionToll-Like Receptor 9ConceptsToll-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 ResearchMeSH KeywordsAdolescentAnimalsChildDiabetes Mellitus, Type 1Fatty Acids, VolatileFemaleGastrointestinal MicrobiomeHumansImmunoglobulin AMaleMiceMice, Inbred NODConceptsType 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 mechanismMiceImmunitySCFA
2018
Distinct neutrophil counts and functions in newly diagnosed type 1 diabetes, latent autoimmune diabetes in adults, and type 2 diabetes
Huang J, Xiao Y, Zheng P, Zhou W, Wang Y, Huang G, Xu A, Zhou Z. Distinct neutrophil counts and functions in newly diagnosed type 1 diabetes, latent autoimmune diabetes in adults, and type 2 diabetes. Diabetes/Metabolism Research And Reviews 2018, 35: e3064. PMID: 30123986, DOI: 10.1002/dmrr.3064.Peer-Reviewed Original ResearchConceptsNeutrophil countType 1 diabetesT1D patientsNeutrophil numbersPhagocytosis rateTitres of autoantibodiesΒ-cell antigensΒ-cell autoimmunityChemokine receptor expressionType 2 diabetesMigration of neutrophilsLADA patientsPositive autoantibodiesAutoimmune diabetesChemokine levelsCD62L expressionT2D patientsClinical parametersNeutrophil migrationHealthy controlsReceptor expressionAnimal modelsDiabetesPatientsDifferent subtypes
2016
Neutrophils in type 1 diabetes
Huang J, Xiao Y, Xu A, Zhou Z. Neutrophils in type 1 diabetes. Journal Of Diabetes Investigation 2016, 7: 652-663. PMID: 27181374, PMCID: PMC5009125, DOI: 10.1111/jdi.12469.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Adhesion MoleculesCell CommunicationCell CountCell DegranulationCytokinesDiabetes Mellitus, Type 1HumansIslets of LangerhansNeutrophilsReactive Oxygen SpeciesConceptsType 1 diabetesImmune cellsDiabetogenic T cell responseAutoimmune type 1 diabetesType 1 diabetes pathogenesisType 1 diabetes developmentΒ-cellsInsulin-producing pancreatic β-cellsProgression of insulitisT cell responsesFirst immune cellsNon-immune cellsImmune cell typesPancreatic β-cellsDendritic cellsDiabetes developmentAutoimmune diseasesDegranulation productsDiabetes pathogenesisExtracellular trapsT cellsDiabetesCell responsesNeutrophilsIslet cells