Maria Bettini

Maria Bettini, PhD

Languages spoken: English

Academic Information

Departments Primary - Pathology

Academic Office Information

Maria.Bettini@path.utah.edu

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 and 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.

Education History

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

Selected Publications

Journal Article

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

Review

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