2024
Tlr9 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 mice
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 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 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 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
Host 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
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 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-1Gut 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 mechanismMiceImmunitySCFA
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 ResearchConceptsType 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
2013
Connective tissue growth factor induces osteogenic differentiation of vascular smooth muscle cells through ERK signaling
HUANG J, HUANG H, WU M, LI J, XIE H, ZHOU H, LIAO E, PENG Y. Connective tissue growth factor induces osteogenic differentiation of vascular smooth muscle cells through ERK signaling. International Journal Of Molecular Medicine 2013, 32: 423-429. PMID: 23722620, DOI: 10.3892/ijmm.2013.1398.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCalcification, PhysiologicCell TransdifferentiationConnective Tissue Growth FactorCore Binding Factor Alpha 1 SubunitExtracellular Signal-Regulated MAP KinasesGene Expression RegulationMiceMuscle, Smooth, VascularMyocytes, Smooth MuscleOsteocytesOsteogenesisSignal TransductionConceptsConnective tissue growth factorTissue growth factorVSMC calcificationRole of CTGFSmooth muscle specific αGrowth factorCalcification of VSMCsVascular smooth muscle cell growthVascular smooth muscle cellsSmooth muscle cell growthPathogenesis of atherosclerosisMouse thoracic aortaSmooth muscle cellsMuscle cell growthERK-specific inhibitorAlkaline phosphataseVascular calcificationExtracellular signal-regulated kinase (ERK) activityThoracic aortaVSMC transdifferentiationBone markersAlizarin Red S stainingTranscription factor 2Primary VSMCsMuscle cells