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 diabetes
2018
TRIF deficiency protects non-obese diabetic mice from type 1 diabetes by modulating the gut microbiota and dendritic cells
Gülden E, Chao C, Tai N, Pearson JA, Peng J, Majewska-Szczepanik M, Zhou Z, Wong FS, Wen L. TRIF deficiency protects non-obese diabetic mice from type 1 diabetes by modulating the gut microbiota and dendritic cells. Journal Of Autoimmunity 2018, 93: 57-65. PMID: 29960834, PMCID: PMC6108920, DOI: 10.1016/j.jaut.2018.06.003.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Vesicular TransportAdoptive TransferAnimalsBacteroidetesBurkholderialesCell ProliferationDendritic CellsDiabetes Mellitus, ExperimentalDisease SusceptibilityFemaleFirmicutesGastrointestinal MicrobiomeGene Expression RegulationLymphocyte ActivationMiceMice, Inbred NODMice, KnockoutMyeloid Differentiation Factor 88Signal TransductionT-LymphocytesToll-Like Receptor 3Toll-Like Receptor 4ConceptsWT NOD miceNOD miceType 1 diabetesGut microbiotaDiabetes developmentDendritic cellsCell activationNon-obese diabetic (NOD) mouse modelMyeloid differentiation primary response gene 88Wild-type NOD miceNon-obese diabetic (NOD) miceToll-like receptor signalingDiabetes susceptibilityStrong inflammatory immune responseDevelopment of diabetesInflammatory immune responseDiabetic mouse modelAdapter-inducing interferonImmune cell activationT cell activationTRIF deficiencyAdaptor protein downstreamFurther immunological analysisHuman T1D.T1D development
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
2015
Maternal Antibiotic Treatment Protects Offspring from Diabetes Development in Nonobese Diabetic Mice by Generation of Tolerogenic APCs
Hu Y, Peng J, Tai N, Hu C, Zhang X, Wong FS, Wen L. Maternal Antibiotic Treatment Protects Offspring from Diabetes Development in Nonobese Diabetic Mice by Generation of Tolerogenic APCs. The Journal Of Immunology 2015, 195: 4176-4184. PMID: 26401004, PMCID: PMC4765177, DOI: 10.4049/jimmunol.1500884.Peer-Reviewed Original ResearchConceptsNOD miceTolerogenic APCsDiabetes developmentT cell-mediated autoimmune diseaseDiabetogenic CD8 T cellsCell-mediated autoimmune diseasePolymyxin BCD8 T cellsNonobese diabetic (NOD) miceType 1 diabetesHost immune systemIslet β-cellsAutoimmune diabetesDifferent time pointsImmune toleranceDiabetic miceAutoimmune diseasesProfound protectionT cellsImmune responseProtective effectCommensal microbiotaGut microbiotaSusceptible individualsCommensal bacteriaThe role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity
Tai N, Wong FS, Wen L. The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Reviews In Endocrine And Metabolic Disorders 2015, 16: 55-65. PMID: 25619480, PMCID: PMC4348024, DOI: 10.1007/s11154-015-9309-0.Peer-Reviewed Original ResearchConceptsGut microbiotaAutoimmune type 1 diabetesType 2 diabetes mellitusInsulin-resistant type 2 diabetesMajor public health concernAltered gut microbiotaDevelopment of T1DType 2 diabetesType 1 diabetesGut microbiota compositionPublic health concernDiabetes mellitusPersistent hyperglycemiaMetabolic disordersRodent modelsMicrobiota compositionType 1ObesityDiabetesHealth concernPotential mechanismsMicrobiotaT2DT1DDisease development