2023
NLRP6 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
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 diabetesToll-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
2018
Toll-like receptor 9 negatively regulates pancreatic islet beta cell growth and function in a mouse model of type 1 diabetes
Liu M, Peng J, Tai N, Pearson JA, Hu C, Guo J, Hou L, Zhao H, Wong FS, Wen L. Toll-like receptor 9 negatively regulates pancreatic islet beta cell growth and function in a mouse model of type 1 diabetes. Diabetologia 2018, 61: 2333-2343. PMID: 30094467, PMCID: PMC6182661, DOI: 10.1007/s00125-018-4705-0.Peer-Reviewed Original ResearchConceptsToll-like receptorsType 1 diabetesRole of TLR9Beta-cell functionNOD miceBeta-cell developmentBeta cellsGlucose toleranceTLR9 antagonistFirst-phase insulin secretory responseInnate immune Toll-like receptorsRole of TLRsImmune Toll-like receptorsWild-type NOD miceType 1 diabetes developmentToll-like receptor 9Absence of TLR9Cell functionIslet beta-cell growthBeta cell numberInsulin secretory responseEnhanced glucose toleranceIslet beta cellsPotential therapeutic targetBeta-cell growthActivation-induced cytidine deaminase deficiency accelerates autoimmune diabetes in NOD mice
Tan Q, Tai N, Li Y, Pearson J, Pennetti S, Zhou Z, Wong FS, Wen L. Activation-induced cytidine deaminase deficiency accelerates autoimmune diabetes in NOD mice. JCI Insight 2018, 3: e95882. PMID: 29321370, PMCID: PMC5821212, DOI: 10.1172/jci.insight.95882.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAutoantibodiesAutoimmunityB-LymphocytesCytidine DeaminaseCytokinesDiabetes Mellitus, Type 1Enzyme ActivationFemaleGene Knockdown TechniquesImmune ToleranceImmunoglobulin AImmunoglobulin GInsulinInterferon-gammaLymph NodesMaleMiceMice, Inbred NODMilkPlacentaPregnancySpleenT-LymphocytesVirulenceConceptsDiabetes developmentB cellsT cellsNOD miceActivation-induced cytidine deaminaseType 1 diabetes developmentAccelerated diabetes developmentAnti-insulin autoantibodiesIFN-γ expressionMore rapid onsetB cell interactionsRole of AIDAccelerated T1DActivation-induced cytidine deaminase (AID) deficiencyAutoimmune diabetesIslet autoimmunityT1D developmentImmune toleranceMaternal IgGT-betRapid onsetPresence of AIDMiceDeaminase deficiencyCD4
2016
Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice
Tai N, Peng J, Liu F, Gulden E, Hu Y, Zhang X, Chen L, Wong FS, Wen L. Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice. Journal Of Experimental Medicine 2016, 213: 2129-2146. PMID: 27621416, PMCID: PMC5030808, DOI: 10.1084/jem.20160526.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigens, BacterialCD8-Positive T-LymphocytesCell DifferentiationDiabetes Mellitus, ExperimentalFemaleGastrointestinal MicrobiomeGlucose-6-PhosphataseLymphocyte ActivationMice, Inbred C57BLMice, Inbred NODMyeloid Differentiation Factor 88PeptidesReceptors, Antigen, T-CellThymus GlandT-Lymphocytes, RegulatoryConceptsCD8 T cellsT cellsCommensal bacteriaSignificant homologyDiabetes developmentGut microbiotaDiabetogenic CD8 T cellsPathogenic CD8 T cellsTransgenic nonobese diabetic miceGut microbesType 1 diabetes developmentIslet-specific glucose-6-phosphatase catalytic subunit-related proteinNovel mechanismNonobese diabetic (NOD) miceInnate immunityBacteriaMolecular mimicryNOD miceIslet autoantigensT1D developmentDiabetic miceMicrobial antigensCellsAnimal modelsHuman studies