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Maria Bettini

Associate Professor of Microbiology and Immunology

Autoimmunity, T cell biology, Tolerance, Metabolism

David Blair


Molecular Biology Program


B.S. East Tennessee State University

Ph.D. Emory University



The ultimate goal of the research in our laboratory is to understand the immunological mechanisms of autoimmunity. We are primarily interested in T cell mediated autoimmunity and mechanisms of T cell function in health and disease. The majority of our work is focused on type 1 autoimmune diabetes, which results from T cell mediated destruction of insulin producing beta cells in the pancreas.  Loss of beta cells leads to dysregulation of glucose metabolism and a life-long dependency on insulin injections. There is no cure for type 1 diabetes, and we still have limited understanding of the immunologic and metabolic dysfunction that ultimately leads to beta cell loss. Members of the laboratory utilize genetically modified mouse models, flow cytometry, transcriptional analysis and metabolic assays to study the interactions between the immune system and metabolism. Our goal is to understand why self-tolerance mechanisms fail in autoimmunity, and whether we can identify immunologic or metabolic pathways that can be manipulated to reverse this process. We are particularly interested in a special population of T cells that can suppress autoimmunity – Foxp3+ regulatory T cells. Regulatory T cells employ multiple mechanisms to maintain immune and metabolic homeostasis, suppress autoimmunity, and aid in tissue repair. Our laboratory has shown that T cell receptor signaling can modulate the type and amplitude of regulatory T cell suppressive mechanisms, which suggests that there are sub-populations of cells with specialized functions. Current work in the lab is focused on further understanding of T cell receptor signaling and downstream suppressive functions in regulatory T cell populations. Additional projects are focused on transcriptional and epigenetic mechanisms associated with chronic T cell activation and inflammation in autoimmunity.


  1. Kong Y, Jing Y, Allard D, Scavuzzo MA, Sprouse ML, Borowiak M, Bettini ML, Bettini MA dormant T-cell population with autoimmune potential exhibits low self-reactivity and infiltrates islets in type 1 diabetes. Eur J Immunol. 2022. PMID: 35389516. 
  2. Lin Y, Perovanovic J, Kong Y, Igyarto BZ, Zurawski S, Tantin D, Zurawski G, Bettini M, Bettini ML. Antibody-Mediated Targeting of a Hybrid-Insulin-Peptide Towards Neonatal Thymic Langerin+ Cells Enhances T Cell Central Tolerance and Delays Autoimmune Diabetes. Diabetes 2022. PMID: 35622068. 
  3. Jing Y, Kong Y, McGinty J, Blahnik-Fagan G, Lee T, Orozco-Figueroa S, Bettini ML, James EA, Bettini MT-Cell Receptor/HLA Humanized Mice Reveal Reduced Tolerance and Increased Immunogenicity of Posttranslationally Modified GAD65 Epitope. Diabetes 2022. PMC9044133. 
  4. Bettini M, Bettini ML. Function, Failure, and the Future Potential of Tregs in Type 1 Diabetes. Diabetes 2021. PMC8275894. 
  5. Boddul SV, Sharma RK, Dubnovitsky A, Raposo B, Gerstner C, Shen Y, Iyer VS, Kasza Z, Kwok WW, Winkler AR, Klareskog L, Malmström V, Bettini M, Wermeling F. In vitro and ex vivo functional characterization of human HLA-DRB1∗04 restricted T cell receptors. J Transl Autoimmun. 2021. PMCID: PMC7980064.
  6. Bettini M, Scavuzzo MA, Liu B, Kolawole E, Guo L, Evavold BD, Borowiak M, Bettini ML. A Critical Insulin TCR Contact Residue Selects High-Affinity and Pathogenic Insulin-Specific T Cells.Diabetes. 2020 Mar;69(3):392-400. PMC7034183.
  7. Liu B, Hood JD, Kolawole EM, Woodruff DM, Vignali DA, Bettini M, Evavold BD. A Hybrid Insulin Epitope Maintains High 2D Affinity for Diabetogenic T Cells in the Periphery.Diabetes. 2020 Mar;69(3):381-391. PMC7034185.
  8. Gu BH, Sprouse ML, Madison MC, Hong MJ, Yuan X, Tung HY, Landers CT, Song LZ, Corry DB, Bettini M, Kheradmand F. A Novel Animal Model of Emphysema Induced by Anti-Elastin Autoimmunity.J Immunol. 2019 Jul 15;203(2):349-359. PMC6688643.
  9. Kong Y, Jing Y, Bettini MGeneration of T Cell Receptor Retrogenic Mice.Curr Protoc Immunol.2019 Jun;125(1):e76. PMC6570547.
  10. Zeng Q, Sun X, Xiao L, Xie Z, Bettini M, Deng T. A Unique Population: Adipose-Resident Regulatory T Cells.Front Immunol. 2018;9:2075. PMC6172295.
  11. Scavuzzo MA, Hill MC, Chmielowiec J, Yang D, Teaw J, Sheng K, Kong Y, Bettini M, Zong C, Martin JF, Borowiak M. Endocrine lineage biases arise in temporally distinct endocrine progenitors during pancreatic morphogenesis.Nat Commun. 2018 Aug 22;9(1):3356. PMC6105717.
  12. Sprouse ML, Shevchenko I, Scavuzzo MA, Joseph F, Lee T, Blum S, Borowiak M, Bettini ML, Bettini MCutting Edge: Low-Affinity TCRs Support Regulatory T Cell Function in Autoimmunity.J Immunol. 2018 Feb 1;200(3):909-914. PMC5962277.
  13. Sprouse ML, Scavuzzo MA, Blum S, Shevchenko I, Lee T, Makedonas G, Borowiak M, Bettini ML, Bettini MHigh self-reactivity drives T-bet and potentiates Treg function in tissue-specific autoimmunity.JCI Insight. 2018 Jan 25;3(2). PMC5821181.
  14. Bettini ML, Bettini MUnderstanding Autoimmune Diabetes through the Prism of the Tri-Molecular Complex.Front Endocrinol (Lausanne). 2017;8:351. PMC5735072.
  15. Lee T, Sprouse ML, Banerjee P, Bettini M, Bettini ML. Ectopic Expression of Self-Antigen Drives Regulatory T Cell Development and Not Deletion of Autoimmune T Cells.J Immunol. 2017 Oct 1;199(7):2270-2278. PMC5605461.
  16. Sprouse ML, Blahnik G, Lee T, Tully N, Benarjee P, James EA, Redondo MJ, Bettini ML, Bettini M.Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs.J Vis Exp. 2017 Sep 10;(127). PMC5752194.
  17. Zhang Q, Chikina M, Szymczak-Workman AL, Horne W, Kolls JK, Vignali KM, Normolle D, Bettini M, Workman CJ, Vignali DAA. LAG3 limits regulatory T cell proliferation and function in autoimmune diabetes.Sci Immunol. 2017 Mar 31;2(9). PMC5609824.
  18. Sprouse ML, Blahnik G, Lee T, Tully N, Banerjee P, James EA, Redondo MJ, Bettini ML, Bettini M.Rapid identification and expression of human TCRs in retrogenic mice.J Immunol Methods.2016 Dec;439:29-36. PMC5439214.
  19. Lee T, Shevchenko I, Sprouse ML, Bettini M, Bettini ML. Retroviral Transduction of Bone Marrow Progenitor Cells to Generate T-cell Receptor Retrogenic Mice.J Vis Exp. 2016 Jul 11;(113). PMC4993443.
  20. Bettini M, Blanchfield L, Castellaw A, Zhang Q, Nakayama M, Smeltzer MP, Zhang H, Hogquist KA, Evavold BD, Vignali DA. TCR affinity and tolerance mechanisms converge to shape T cell diabetogenic potential.J Immunol. 2014 Jul 15;193(2):571-9. PMC4082738.
  21. Bettini ML, Bettini M, Nakayama M, Guy CS, Vignali DA. Generation of T cell receptor-retrogenic mice: improved retroviral-mediated stem cell gene transfer. Nat Protoc. 2013 Oct;8(10):1837-40. PMC3832243. 
  22. Bettini ML, Bettini M, Vignali DA. T-cell receptor retrogenic mice: a rapid, flexible alternative to T-cell receptor transgenic mice. Immunology. 2012 Jul;136(3):265-72. PMC3385026. 
  23. Bettini M, Castellaw AH, Lennon GP, Burton AR, Vignali DA. Prevention of autoimmune diabetes by ectopic pancreatic β-cell expression of interleukin-35. Diabetes. 2012 Jun;61(6):1519-26. PMC3357277. 
  24. Bettini ML, Pan F, Bettini M, Finkelstein D, Rehg JE, Floess S, Bell BD, Ziegler SF, Huehn J, Pardoll DM, Vignali DA. Loss of epigenetic modification driven by the Foxp3 transcription factor leads to regulatory T cell insufficiency. Immunity. 2012 May 25;36(5):717-30. PMC3361541. 
  25. Bettini M, Vignali DA. T cell-driven initiation and propagation of autoimmune diabetes. Curr Opin Immunol. 2011 Dec;23(6):754-60. PMC3232326. 
  26. Bettini M, Szymczak-Workman AL, Forbes K, Castellaw AH, Selby M, Pan X, Drake CG, Korman AJ, Vignali DA. Cutting edge: accelerated autoimmune diabetes in the absence of LAG-3. J Immunol.2011 Oct 1;187(7):3493-8. PMC3178660. 
  27. Workman CJ, Collison LW, Bettini M, Pillai MR, Rehg JE, Vignali DA. In vivo Treg suppression assays. Methods Mol Biol. 2011;707:119-56. PMC3049949. 
  28. Bettini M, Vignali DA. Regulatory T cells and inhibitory cytokines in autoimmunity. Curr Opin Immunol. 2009 Dec;21(6):612-8. PMC2787714. 
  29. Lennon GP, Bettini M, Burton AR, Vincent E, Arnold PY, Santamaria P, Vignali DA. T cell islet accumulation in type 1 diabetes is a tightly regulated, cell-autonomous event. Immunity. 2009 Oct 16;31(4):643-53. PMC2763021. 
  30. Bettini M, Rosenthal K, Evavold BD. Pathogenic MOG-reactive CD8+ T cells require MOG-reactive CD4+ T cells for sustained CNS inflammation during chronic EAE. J Neuroimmunol. 2009 Aug 18;213(1-2):60-8. PMCID: PMC2752735. 
  31. Zakharova M (Bettini M), Ziegler HK. Paradoxical anti-inflammatory actions of TNF-alpha: inhibition of IL-12 and IL-23 via TNF receptor 1 in macrophages and dendritic cells. J Immunol. 2005 Oct 15;175(8):5024-33. PMID: 16210605.
Last Updated: 7/15/22