Maria Bettini

Maria Bettini, PhD

Languages spoken: English

Academic Information

Departments Primary - Pathology

Lab

Our group has been working to understand how T cell receptor guides T cell fate decisions of autoimmune and regulatory Foxp3+ T cells. T cell responses in autoimmunity develop under a unique set of conditions: relatively low TCR affinity, lack of danger signals, and chronic antigen stimulation. We are trying to understand how autoimmune T cells and suppressive regulatory T cells navigate these conditions to persist or fail.

Members of my laboratory utilize genetically modified mouse models, multi-color flow cytometry, high resolution imaging, single cell transcriptomics and epigenetic profiling to study autoimmune and regulatory T cell function. We have made several key observations regarding the function of Foxp3+ T cells in the context of autoimmune type 1 diabetes. Foxp3+ regulatory T cells employ multiple mechanisms to maintain immune and metabolic homeostasis, suppress autoimmunity, and aid in tissue repair. T cell receptor signaling and cellular interactions with tissue and effector T cells converge to guide Treg functions that are specialized for the tissue site and inflammatory context. Current work in the lab is focused on how Tregs integrate T cell receptor signaling with tissue-derived cues to modulate their suppressive functional program. Additional projects are focused on transcriptional and epigenetic mechanisms associated with autoimmune T cell function, autoimmune T cell memory, and T cell exhaustion in chronic inflammation.

Current ongoing projects:

• T cell fate decisions and response to immune therapies

• Epigenetic pre-programming of autoimmune T cells

• Mechanisms of Foxp3 Regulatory T cell persistence, stability, and function in autoimmunity

• Metabolic manipulation of regulatory T cells for improved immunotherapy

• Antigen presenting T cells

Education History

Undergraduate East Tennessee State University
 BS
Doctoral Training Emory University
 PhD
Post Graduate Training Emory University
 Postdoctoral Associate
Post Graduate Training St. Jude Children¿s Research Hospital
 Postdoctoral Fellow

Selected Publications

Journal Article

  1. Workman CJ, Collison LW, Bettini M, Pillai MR, Rehg JE, Vignali D (2011). In vivo Treg suppression assays. Methods in molecular biology (Clifton, N.J.),
  2. Bettini M, Castellaw AH, Lennon GP, Burton AR, Vignali D (2012). Prevention of autoimmune diabetes by ectopic pancreatic beta-cell expression of interleukin-35. Diabetes, 61(6), 1519-26.
  3. Bettini M, Rosenthal K, Evavold B (2009). Pathogenic MOG-reactive CD8+ T cells require MOG-reactive CD4+ T cells for sustained CNS inflammation during chronic EAE. Journal of neuroimmunology, 213(1-2), 60-8.
  4. Zakharova M, Ziegler H (2005). Paradoxical anti-inflammatory actions of TNF-alpha: inhibition of IL-12 and IL-23 via TNF receptor 1 in macrophages and dendritic cells. Journal of immunology (Baltimore, Md., 175(8), 5024-33.
  5. Bettini M, Szymczak-Workman AL, Forbes K, Castellaw AH, Selby M, Pan X, Drake CG, Korman AJ, Vignali D (2011). Cutting edge: accelerated autoimmune diabetes in the absence of LAG-3. Journal of immunology (Baltimore, Md., 187(7), 3493-8.
  6. Bettini M, Blanchfield L, Castellaw A, Zhang Q, Nakayama M, Smeltzer MP, Zhang H, Hogquist KA, Evavold BD, Vignali D (2014). TCR affinity and tolerance mechanisms converge to shape T cell diabetogenic potential. Journal of immunology (Baltimore, Md., 193(2), 571-9.
  7. Lee T, Sprouse ML, Banerjee P, Bettini M, Bettini M (2017). Ectopic Expression of Self-Antigen Drives Regulatory T Cell Development and Not Deletion of Autoimmune T Cells. Journal of immunology (Baltimore, Md., 199(7), 2270-2278.
  8. Gu BH, Sprouse ML, Madison MC, Hong MJ, Yuan X, Tung HY, Landers CT, Song LZ, Corry DB, Bettini M, Kheradmand (2019). A Novel Animal Model of Emphysema Induced by Anti-Elastin Autoimmunity. Journal of immunology (Baltimore, Md.,
  9. Sprouse ML, Shevchenko I, Scavuzzo MA, Joseph F, Lee T, Blum S, Borowiak M, Bettini ML, Bettini (2018). Cutting Edge: Low-Affinity TCRs Support Regulatory T Cell Function in Autoimmunity. Journal of immunology (Baltimore, Md.,
  10. Sprouse ML, Blahnik G, Lee T, Tully N, Banerjee P, James EA, Redondo MJ, Bettini ML, Bettini (2016). Rapid identification and expression of human TCRs in retrogenic mice. Journal of immunological methods, 439, 29-36.
  11. Lennon GP, Bettini M, Burton AR, Vincent E, Arnold PY, Santamaria P, Vignali D (2009). T cell islet accumulation in type 1 diabetes is a tightly regulated, cell-autonomous event. Immunity, 31(4), 643-53.
  12. Bettini ML, Pan F, Bettini M, Finkelstein D, Rehg JE, Floess S, Bell BD, Ziegler SF, Huehn J, Pardoll DM, Vignali D (2012). Loss of epigenetic modification driven by the Foxp3 transcription factor leads to regulatory T cell insufficiency. Immunity, 36(5), 717-30.
  13. Bettini ML, Bettini M, Nakayama M, Guy CS, Vignali D (2013). Generation of T cell receptor-retrogenic mice: improved retroviral-mediated stem cell gene transfer. Nature protocols, 8(10), 1837-40.
  14. Kong Y, Jing Y, Bettini (2019). Generation of T cell receptor retrogenic mice. Current protocols in immunology,
  15. Lee T, Shevchenko I, Sprouse ML, Bettini M, Bettini M (2016). Retroviral Transduction of Bone Marrow Progenitor Cells to Generate T-cell Receptor Retrogenic Mice.LID - 10.3791/54196 [doi]. Journal of visualized experiments, (113),
  16. Sprouse ML, Blahnik G, Lee T, Tully N, Benarjee P, James EA, Redondo MJ, Bettini ML, Bettini (2017). Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs.LID - 10.3791/55379 [doi]. Journal of visualized experiments, (127),
  17. Scavuzzo MA, Hill MC, Chmielowiec J, Yang D, Teaw J, Sheng K, Kong Y, Bettini M, Zong C, Martin JF, Borowiak (2018). Endocrine lineage biases arise in temporally distinct endocrine progenitors during pancreatic morphogenesis. Nature communications,
  18. Sprouse ML, Scavuzzo MA, Blum S, Shevchenko I, Lee T, Makedonas G, Borowiak M, Bettini ML, Bettini (2018). High self-reactivity drives T-bet and potentiates Treg function in tissue-specific autoimmunity. JCI insight,
  19. Zhang Q, Chikina M, Szymczak-Workman AL, Horne W, Kolls JK, Vignali KM, Normolle D, Bettini M, Workman CJ, Vignali DA (2017). LAG3 limits regulatory T cell proliferation and function in autoimmune diabetes.LID - eaah4569 [pii]LID - 10.1126/sciimmunol.aah4569 [doi]. Science immunology, 2(9),
  20. Raugh A, Jing Y, Bettini ML, Bettini (2023). The amphiregulin/EGFR axis has limited contribution in controlling autoimmune diabetes. Scientific reports, 13(1), 18653.
  21. Jing Y, Kong Y, McGinty J, Blahnik-Fagan G, Lee T, Orozco-Figueroa S, Bettini ML, James EA, Bettini (2022). T-Cell Receptor/HLA Humanized Mice Reveal Reduced Tolerance and Increased Immunogenicity of Posttranslationally Modified GAD65 Epitope. Diabetes, 71(5), 1012-1022.
  22. Kong Y, Jing Y, Allard D, Scavuzzo MA, Sprouse ML, Borowiak M, Bettini ML, Bettini (2022). A dormant T-cell population with autoimmune potential exhibits low self-reactivity and infiltrates islets in type 1 diabetes. European journal of immunology, 52(7), 1158-1170.
  23. Bettini M, Scavuzzo MA, Liu B, Kolawole E, Guo L, Evavold BD, Borowiak M, Bettini M (2020). A Critical Insulin TCR Contact Residue Selects High-Affinity and Pathogenic Insulin-Specific T Cells. Diabetes, 69(3), 392-400.
  24. Ronco C, Tetta C, Lupi A, Galloni E, Bettini MC, Sereni L, Mariano F, DeMartino A, Montrucchio G, Camussi (1995). Removal of platelet-activating factor in experimental continuous arteriovenous hemofiltration. Critical care medicine, 23(1), 99-107.
  25. Liu B, Hood JD, Kolawole EM, Woodruff DM, Vignali DA, Bettini M, Evavold B (2020). A Hybrid Insulin Epitope Maintains High 2D Affinity for Diabetogenic T Cells in the Periphery. Diabetes, 69(3), 381-391.
  26. Lin Y, Perovanovic J, Kong Y, Igyarto BZ, Zurawski S, Tantin D, Zurawski G, Bettini M, Bettini M (2022). Antibody-Mediated Targeting of a Hybrid Insulin Peptide Toward Neonatal Thymic Langerin-Positive Cells Enhances T-Cell Central Tolerance and Delays Autoimmune Diabetes. Diabetes, 71(8), 1735-1745.
  27. 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 (2021). In vitro and ex vivo functional characterization of human HLA-DRB1¿04 restricted T cell receptors. Journal of translational autoimmunity, 4, 100087.

Review

  1. Bettini M, Vignali DA (2009). Regulatory T cells and inhibitory cytokines in autoimmunity. [Review]. Curr Opin Immunol, 21, (6), 612-8.
  2. Bettini M, Vignali DA (2011). T cell-driven initiation and propagation of autoimmune diabetes. [Review]. Curr Opin Immunol, 23, (6), 754-60.
  3. Bettini ML, Bettini M, Vignali D (2012). T-cell receptor retrogenic mice: a rapid, flexible alternative to T-cell receptor transgenic mice. Immunology, 136(3), 265-72.
  4. Bettini ML, Bettini (2017). Understanding Autoimmune Diabetes through the Prism of the Tri-Molecular Complex. Frontiers in endocrinology, 8, 351.
  5. Zeng Q, Sun X, Xiao L, Xie Z, Bettini M, Deng (2018). A Unique Population: Adipose-Resident Regulatory T Cells. Frontiers in immunology, 9, 2075.
  6. Bettini M, Bettini M (2021). Function, Failure, and the Future Potential of Tregs in Type 1 Diabetes. Diabetes, 70(6), 1211-1219.
  7. Raugh A, Allard D, Bettini (2022). Nature vs. nurture: FOXP3, genetics, and tissue environment shape Treg function. Frontiers in immunology, 13, 911151.