Li Wen, MD, PhD
Research & Publications
Biography
News
Research Summary
Our research interest lies mainly in autoimmunity, in particular the immunology of type 1 diabetes. Using different animal models, my research group has been trying to understand why immune cells attack insulin producing islet beta cells and how we can prevent this attack and if we can reverse the autoimmune destruction after the disease onset. Our current research topics include 1) the role of innate immunity in type 1 diabetes; 2) the role of gut microbiota in diabetes; 3) the role of B lymphocytes in diabetes; 4) the role of dendritic cells and innate immunity in obesity and diabetes; 5) the role of the inflammasome in diabetes; 6) the role of innate and adaptive immunity in skin allergy; 7) the role of innate and adaptive immunity in liver immunology.
Coauthors
Research Interests
Antigen-Presenting Cells; Autoimmune Diseases; Diabetes Mellitus, Type 1; Hypersensitivity; Immune Tolerance; Immunity, Innate; Islets of Langerhans; Liver; Obesity; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Antigens, CD20; T-Lymphocytes, Regulatory; Toll-Like Receptors; Immunity, Humoral; Inflammasomes; Microbiota
Selected Publications
- Innate immunity and intestinal microbiota in the development of Type 1 diabetes.Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu C, Wong FS, Szot GL, Bluestone JA, Gordon JI, Chervonsky AV. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 2008, 455: 1109-13. PMID: 18806780, PMCID: PMC2574766, DOI: 10.1038/nature07336.
- Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice.Hu CY, Rodriguez-Pinto D, Du W, Ahuja A, Henegariu O, Wong FS, Shlomchik MJ, Wen L. Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. The Journal Of Clinical Investigation 2007, 117: 3857-67. PMID: 18060033, PMCID: PMC2096456, DOI: 10.1172/JCI32405.
- TGF-beta signaling is required for the function of insulin-reactive T regulatory cells.Du W, Wong FS, Li MO, Peng J, Qi H, Flavell RA, Sherwin R, Wen L. TGF-beta signaling is required for the function of insulin-reactive T regulatory cells. The Journal Of Clinical Investigation 2006, 116: 1360-70. PMID: 16670772, PMCID: PMC1451206, DOI: 10.1172/JCI27030.
- B cells in autoimmune diabetes.Wong FS, Wen L. B cells in autoimmune diabetes. The Review Of Diabetic Studies : RDS 2005, 2: 121-35. PMID: 17491687, PMCID: PMC1783559, DOI: 10.1900/RDS.2005.2.121.
- The influence of the major histocompatibility complex on development of autoimmune diabetes in RIP-B7.1 mice.Wong FS, Du W, Thomas IJ, Wen L. The influence of the major histocompatibility complex on development of autoimmune diabetes in RIP-B7.1 mice. Diabetes 2005, 54: 2032-40. PMID: 15983204, DOI: 10.2337/diabetes.54.7.2032.
- Cellular and humoral immune responses in the early stages of diabetic nephropathy in NOD mice.Xiao X, Ma B, Dong B, Zhao P, Tai N, Chen L, Wong FS, Wen L. Cellular and humoral immune responses in the early stages of diabetic nephropathy in NOD mice. Journal Of Autoimmunity 2009, 32: 85-93. PMID: 19200691, DOI: 10.1016/j.jaut.2008.12.003.
- Activation of insulin-reactive CD8 T-cells for development of autoimmune diabetes.Wong FS, Siew LK, Scott G, Thomas IJ, Chapman S, Viret C, Wen L. Activation of insulin-reactive CD8 T-cells for development of autoimmune diabetes. Diabetes 2009, 58: 1156-64. PMID: 19208910, PMCID: PMC2671054, DOI: 10.2337/db08-0800.
- Inflammatory regulation by TLR3 in acute hepatitis.Xiao X, Zhao P, Rodriguez-Pinto D, Qi D, Henegariu O, Alexopoulou L, Flavell RA, Wong FS, Wen L. Inflammatory regulation by TLR3 in acute hepatitis. Journal Of Immunology (Baltimore, Md. : 1950) 2009, 183: 3712-9. PMID: 19710451, PMCID: PMC3787866, DOI: 10.4049/jimmunol.0901221.
- IL-10-conditioned dendritic cells prevent autoimmune diabetes in NOD and humanized HLA-DQ8/RIP-B7.1 mice.Tai N, Yasuda H, Xiang Y, Zhang L, Rodriguez-Pinto D, Yokono K, Sherwin R, Wong FS, Nagata M, Wen L. IL-10-conditioned dendritic cells prevent autoimmune diabetes in NOD and humanized HLA-DQ8/RIP-B7.1 mice. Clinical Immunology (Orlando, Fla.) 2011, 139: 336-49. PMID: 21458378, DOI: 10.1016/j.clim.2011.03.003.
- The dual effects of B cell depletion on antigen-specific T cells in BDC2.5NOD mice.Xiang Y, Peng J, Tai N, Hu C, Zhou Z, Wong FS, Wen L. The dual effects of B cell depletion on antigen-specific T cells in BDC2.5NOD mice. Journal Of Immunology (Baltimore, Md. : 1950) 2012, 188: 4747-58. PMID: 22490442, PMCID: PMC4361183, DOI: 10.4049/jimmunol.1103055.
- The role of Gr1+ cells after anti-CD20 treatment in type 1 diabetes in nonobese diabetic mice.Hu C, Du W, Zhang X, Wong FS, Wen L. The role of Gr1+ cells after anti-CD20 treatment in type 1 diabetes in nonobese diabetic mice. Journal Of Immunology (Baltimore, Md. : 1950) 2012, 188: 294-301. PMID: 22140261, PMCID: PMC4361178, DOI: 10.4049/jimmunol.1101590.
- Role of IRAK-M in alcohol induced liver injury.Wang Y, Hu Y, Chao C, Yuksel M, Colle I, Flavell RA, Ma Y, Yan H, Wen L. Role of IRAK-M in alcohol induced liver injury. PloS One 2013, 8: e57085. PMID: 23437317, PMCID: PMC3578822, DOI: 10.1371/journal.pone.0057085.
- Combination treatment with anti-CD20 and oral anti-CD3 prevents and reverses autoimmune diabetes.Hu C, Ding H, Zhang X, Wong FS, Wen L. Combination treatment with anti-CD20 and oral anti-CD3 prevents and reverses autoimmune diabetes. Diabetes 2013, 62: 2849-58. PMID: 23447122, PMCID: PMC3717853, DOI: 10.2337/db12-1175.
- TLR9 deficiency promotes CD73 expression in T cells and diabetes protection in nonobese diabetic mice.Tai N, Wong FS, Wen L. TLR9 deficiency promotes CD73 expression in T cells and diabetes protection in nonobese diabetic mice. Journal Of Immunology (Baltimore, Md. : 1950) 2013, 191: 2926-37. PMID: 23956420, PMCID: PMC3788667, DOI: 10.4049/jimmunol.1300547.
- IRAK-M deficiency promotes the development of type 1 diabetes in NOD mice.Tan Q, Majewska-Szczepanik M, Zhang X, Szczepanik M, Zhou Z, Wong FS, Wen L. IRAK-M deficiency promotes the development of type 1 diabetes in NOD mice. Diabetes 2014, 63: 2761-75. PMID: 24696448, PMCID: PMC4113073, DOI: 10.2337/db13-1504.
- Long term effect of gut microbiota transfer on diabetes development.Peng J, Narasimhan S, Marchesi JR, Benson A, Wong FS, Wen L. Long term effect of gut microbiota transfer on diabetes development. Journal Of Autoimmunity 2014, 53: 85-94. PMID: 24767831, PMCID: PMC4361177, DOI: 10.1016/j.jaut.2014.03.005.
- NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets.Hu C, Ding H, Li Y, Pearson JA, Zhang X, Flavell RA, Wong FS, Wen L. NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 11318-23. PMID: 26305961, PMCID: PMC4568693, DOI: 10.1073/pnas.1513509112.
- 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. Journal Of Immunology (Baltimore, Md. : 1950) 2015, 195: 4176-84. PMID: 26401004, PMCID: PMC4765177, DOI: 10.4049/jimmunol.1500884.
- The Gut Microbiome in the NOD Mouse.Peng J, Hu Y, Wong FS, Wen L. The Gut Microbiome in the NOD Mouse. Methods In Molecular Biology (Clifton, N.J.) 2016, 1433: 169-77. PMID: 27032947, DOI: 10.1007/7651_2016_331.
- Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production.Majewska-Szczepanik M, Askenase PW, Lobo FM, Marcińska K, Wen L, Szczepanik M. Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production. The Journal Of Allergy And Clinical Immunology 2016, 138: 262-273.e6. PMID: 26810716, PMCID: PMC5278675, DOI: 10.1016/j.jaci.2015.11.018.
- Different immunological responses to early-life antibiotic exposure affecting autoimmune diabetes development in NOD mice.Hu Y, Jin P, Peng J, Zhang X, Wong FS, Wen L. Different immunological responses to early-life antibiotic exposure affecting autoimmune diabetes development in NOD mice. Journal Of Autoimmunity 2016, 72: 47-56. PMID: 27178773, PMCID: PMC4958594, DOI: 10.1016/j.jaut.2016.05.001.
- The role of lymphocyte subsets in accelerated diabetes in nonobese diabetic-rat insulin promoter-B7-1 (NOD-RIP-B7-1) mice.Wong FS, Visintin I, Wen L, Granata J, Flavell R, Janeway CA. The role of lymphocyte subsets in accelerated diabetes in nonobese diabetic-rat insulin promoter-B7-1 (NOD-RIP-B7-1) mice. The Journal Of Experimental Medicine 1998, 187: 1985-93. PMID: 9625758, PMCID: PMC2212360, DOI: 10.1084/jem.187.12.1985.
- Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library.Wong FS, Karttunen J, Dumont C, Wen L, Visintin I, Pilip IM, Shastri N, Pamer EG, Janeway CA. Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library. Nature Medicine 1999, 5: 1026-31. PMID: 10470079, DOI: 10.1038/12465.
- Norovirus Changes Susceptibility to Type 1 Diabetes by Altering Intestinal Microbiota and Immune Cell Functions.Pearson JA, Tai N, Ekanayake-Alper DK, Peng J, Hu Y, Hager K, Compton S, Wong FS, Smith PC, Wen L. Norovirus Changes Susceptibility to Type 1 Diabetes by Altering Intestinal Microbiota and Immune Cell Functions. Frontiers In Immunology 2019, 10: 2654. PMID: 31798584, PMCID: PMC6863139, DOI: 10.3389/fimmu.2019.02654.
- A predictive CD8+ T cell phenotype for T1DM progression.Wong FS, Wen L. A predictive CD8+ T cell phenotype for T1DM progression. Nature Reviews. Endocrinology 2020, 16: 198-199. PMID: 32051538, PMCID: PMC8258660, DOI: 10.1038/s41574-020-0330-3.
- Mouse Models of Autoimmune Diabetes: The Nonobese Diabetic (NOD) Mouse.Chen D, Thayer TC, Wen L, Wong FS. Mouse Models of Autoimmune Diabetes: The Nonobese Diabetic (NOD) Mouse. Methods In Molecular Biology (Clifton, N.J.) 2020, 2128: 87-92. PMID: 32180187, PMCID: PMC8253669, DOI: 10.1007/978-1-0716-0385-7_6.
- Gut 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 FS, 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.
- Immunoglobulin synthesis and generalized autoimmunity in mice congenitally deficient in alpha beta(+) T cells.Wen L, Roberts SJ, Viney JL, Wong FS, Mallick C, Findly RC, Peng Q, Craft JE, Owen MJ, Hayday AC. Immunoglobulin synthesis and generalized autoimmunity in mice congenitally deficient in alpha beta(+) T cells. Nature 1994, 369: 654-8. PMID: 8208291, DOI: 10.1038/369654a0.
- CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells.Wong FS, Visintin I, Wen L, Flavell RA, Janeway CA. CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells. The Journal Of Experimental Medicine 1996, 183: 67-76. PMID: 8551245, PMCID: PMC2192404, DOI: 10.1084/jem.183.1.67.
- Murine lupus in the absence of alpha beta T cells.Peng SL, Madaio MP, Hughes DP, Crispe IN, Owen MJ, Wen L, Hayday AC, Craft J. Murine lupus in the absence of alpha beta T cells. Journal Of Immunology (Baltimore, Md. : 1950) 1996, 156: 4041-9. PMID: 8621947.
- Altered 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 And Metabolism 2020, 105 PMID: 32860693, PMCID: PMC7549925, DOI: 10.1210/clinem/dgaa590.
- Crosstalk between circadian rhythms and the microbiota.Pearson JA, Wong FS, Wen L. Crosstalk between circadian rhythms and the microbiota. Immunology 2020, 161: 278-290. PMID: 33090484, PMCID: PMC7692254, DOI: 10.1111/imm.13278.
- Differentiating MHC-Dependent and -Independent Mechanisms of Lymph Node Stromal Cell Regulation of Proinsulin-Specific CD8+ T Cells in Type 1 Diabetes.Thayer TC, Davies J, Pearson JA, Hanna SJ, Wen L, Wong FS. Differentiating MHC-Dependent and -Independent Mechanisms of Lymph Node Stromal Cell Regulation of Proinsulin-Specific CD8+ T Cells in Type 1 Diabetes. Diabetes 2021, 70: 529-537. PMID: 33122391, PMCID: PMC8176215, DOI: 10.2337/db19-1050.
- 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 2021, 70: 504-515. PMID: 33154070, PMCID: PMC7881860, DOI: 10.2337/db20-0373.
- Insulin-Reactive T Cells Convert Diabetogenic Insulin-Reactive VH125 B Cells Into Tolerogenic Cells by Reducing Germinal Center T:B Cell Interactions in NOD Mice.Pearson JA, Li Y, Majewska-Szczepanik M, Guo J, Zhang L, Liu Y, Wong FS, Wen L. Insulin-Reactive T Cells Convert Diabetogenic Insulin-Reactive VH125 B Cells Into Tolerogenic Cells by Reducing Germinal Center T:B Cell Interactions in NOD Mice. Frontiers In Immunology 2020, 11: 585886. PMID: 33262765, PMCID: PMC7688534, DOI: 10.3389/fimmu.2020.585886.
- Toll-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.
- Innate 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 2022, 38: e3480. PMID: 34156143, PMCID: PMC8813511, DOI: 10.1002/dmrr.3480.
- Inflammasomes and Type 1 Diabetes.Pearson JA, Wong FS, Wen L. Inflammasomes and Type 1 Diabetes. Frontiers In Immunology 2021, 12: 686956. PMID: 34177937, PMCID: PMC8219953, DOI: 10.3389/fimmu.2021.686956.
- 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.
- Circadian Rhythm Modulation of Microbes During Health and Infection.Pearson JA, Voisey AC, Boest-Bjerg K, Wong FS, Wen L. Circadian Rhythm Modulation of Microbes During Health and Infection. Frontiers In Microbiology 2021, 12: 721004. PMID: 34512600, PMCID: PMC8430216, DOI: 10.3389/fmicb.2021.721004.
- Obesity aggravates contact hypersensitivity reaction in mice.Majewska-Szczepanik M, Kowalczyk P, Marcińska K, Strzępa A, Lis GJ, Wong FS, Szczepanik M, Wen L. Obesity aggravates contact hypersensitivity reaction in mice. Contact Dermatitis 2022 PMID: 35234303, DOI: 10.1111/cod.14088.
- Editorial: Immunopathology of Type 1 Diabetes.Green EA, Cooke AC, Piganelli JD, Richardson SJ, Wen L, Wong FS. Editorial: Immunopathology of Type 1 Diabetes. Frontiers In Immunology 2022, 13: 852963. PMID: 35359940, PMCID: PMC8960371, DOI: 10.3389/fimmu.2022.852963.
- IgM-associated gut bacteria in obesity and type 2 diabetes in C57BL/6 mice and humans.Pearson JA, Ding H, Hu C, Peng J, Galuppo B, Wong FS, Caprio S, Santoro N, Wen L. IgM-associated gut bacteria in obesity and type 2 diabetes in C57BL/6 mice and humans. Diabetologia 2022 PMID: 35587276, DOI: 10.1007/s00125-022-05711-8.
Clinical Trials
Conditions | Study Title |
---|---|
Diabetes Mellitus - Type 2 | Onxy-Sorghum Study: Investigating the effect of Onyx Sorghum on blood glucose control in individuals with type 2 diabetes |