Matthew L. Bettini

Matthew L. Bettini, PhD, MS

Languages spoken: English

Academic Information

Departments Primary - Pathology

Lab

Dr. Matt Bettini’s work has focused on understanding neonatal tolerance to organ specific antigens and extended-self (microbiota). The mechanisms by which tolerance is established early in life is still unclear. His work seeks to understand how various antigen presenting cells found within the thymus can strengthen central tolerance mechanisms including deletion of auto reactive cells and regulatory T cell development. Some of these APCs migrate from the periphery while others are resident and each have a unique role. More recently, Dr. Bettini has begun exploring the role of ITAMs in CAR T cell signaling and function. Overall, Dr. Bettini’s laboratory is dedicated to understanding early T cell fate decisions of selection, Treg development and function.

Research Statement

The focus of my research is mechanisms of central tolerance with 1) self and 2) extended-self antigens. A 3rd area of research is focused on CAR signaling as it pertains to persistence and function.

Current available projects are 1) Investigating the role of early exposure to microflora in central tolerance and it’s impact on Type 1 Diabetes. 2) Neonatal tolerance to pancreatic antigens by targeting thymic and peripheral DCs.

Education History

Undergraduate Furman University
 BS
Graduate Training Georgia State University
 MS
Doctoral Training Emory University
 PhD
Research Fellow St. Jude Children's Research Hospital
 Postdoctoral Research Fellow

Selected Publications

Journal Article

  1. Paust S, Bettini M (2015). Daring to learn from humanized mice. Blood, 125(25), 3829-31.
  2. Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, Bettini ML, Gravano DM, Vogel P, Liu CL, Tangsombatvisit S, Grosso JF, Netto G, Smeltzer MP, Chaux A, Utz PJ, Workman CJ, Pardoll DM, Korman AJ, Drake CG, Vignali DA (2012). Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res, 72(4), 917-27.
  3. 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.
  4. Bettini M, Bettini M (2021). Function, Failure, and the Future Potential of Tregs in Type 1 Diabetes. Diabetes, 70(6), 1211-1219.
  5. Wang H, Holst J, Woo SR, Guy C, Bettini M, Wang Y, Shafer A, Naramura M, Mingueneau M, Dragone LL, Hayes SM, Malissen B, Band H, Vignali D (2010). Tonic ubiquitylation controls T-cell receptor:CD3 complex expression during T-cell development. The EMBO journal, 29(7), 1285-98.
  6. Bettini M, Xi H, Kersh G (2003). T cell stimulation in the absence of exogenous antigen: a T cell signal is induced by both MHC-dependent and -independent mechanisms. European journal of immunology, 33(11), 3109-16.
  7. Kucharzik T, Hudson JT 3rd, Lugering A, Abbas JA, Bettini M, Lake JG, Evans ME, Ziegler TR, Merlin D, Madara JL, Williams I (2005). Acute induction of human IL-8 production by intestinal epithelium triggers neutrophil infiltration without mucosal injury. Gut, 54(11), 1565-72.
  8. Bettini M, Xi H, Milbrandt J, Kersh G (2002). Thymocyte development in early growth response gene 1-deficient mice. Journal of immunology (Baltimore, Md., 169(4), 1713-20.
  9. Bettini ML, Guy C, Dash P, Vignali KM, Hamm DE, Dobbins J, Gagnon E, Thomas PG, Wucherpfennig KW, Vignali D (2014). Membrane association of the CD3epsilon signaling domain is required for optimal T cell development and function. Journal of immunology (Baltimore, Md., 193(1), 258-67.
  10. Bettini ML, Chou PC, Guy CS, Lee T, Vignali KM, Vignali DA (2017). Cutting Edge: CD3 ITAM Diversity Is Required for Optimal TCR Signaling and Thymocyte Development. Journal of immunology (Baltimore, Md., 199(5), 1555-1560.
  11. Lee T, Sprouse ML, Banerjee P, Bettini, 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.
  12. 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., 200(3), 909-914.
  13. Sprouse ML, Blahnik G, Lee T, Tully N, Banerjee P, James EA, Redondo MJ, Bettini ML, Bettin (2016). Rapid identification and expression of human TCRs in retrogenic mice. Journal of immunological methods, 439, 29-36.
  14. Delgoffe GM, Woo SR, Turnis ME, Gravano DM, Guy C, Overacre AE, Bettini ML, Vogel P, Finkelstein D, Bonnevier J, Workman CJ, Vignali D (2013). Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis. Nature, 501(7466), 252-6.
  15. Zegarra-Ruiz DF, Kim DV, Norwood K, Kim M, Wu WH, Saldana-Morales FB, Hill AA, Majumdar S, Orozco S, Bell R, Round JL, Longman RS, Egawa T, Bettini ML, Diehl G (2021). Thymic development of gut-microbiota-specific T cells. Nature, 594(7863), 413-417.
  16. Bettini ML, Kersh G (2007). MAP kinase phosphatase activity sets the threshold for thymocyte positive selection. Proceedings of the National Academy of Sciences of the United States of America, 104(41), 16257-62.
  17. 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.
  18. Delgoffe GM, Bettini ML, Vignali D (2012). Identity crisis: it's not just Foxp3 anymore. Immunity, 37(5), 759-61.
  19. Kim M, Galan C, Hill AA, Wu WJ, Fehlner-Peach H, Song HW, Schady D, Bettini ML, Simpson KW, Longman RS, Littman DR, Diehl G (2018). Critical Role for the Microbiota in CX3CR1+ Intestinal Mononuclear Phagocyte Regulation of Intestinal T Cell Responses. Immunity, 49(1), 151-163.e5.
  20. Shrestha AK, Bettini ML, Menon RT, Gopal VYN, Huang S, Edwards DP, Pammi M, Barrios R, Shivanna (2019). Consequences of early postnatal lipopolysaccharide exposure on developing lungs in mice. American journal of physiology. Lung cellular and molecular physiology, 316(1), L229-L244.
  21. Guy CS, Vignali KM, Temirov J, Bettini ML, Overacre AE, Smeltzer M, Zhang H, Huppa JB, Tsai YH, Lobry C, Xie J, Dempsey PJ, Crawford HC, Aifantis I, Davis MM, Vignali D (2013). Distinct TCR signaling pathways drive proliferation and cytokine production in T cells. Nature immunology, 14(3), 262-70.
  22. Bettini ML, Bettini, 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.
  23. Lee T, Shevchenko I, Sprouse ML, Bettini, 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),
  24. Bettini ML, Bettini (2017). Understanding Autoimmune Diabetes through the Prism of the Tri-Molecular Complex. Frontiers in endocrinology, 8, 351.
  25. Ramstead AG, Wallace JA, Lee SH, Bauer KM, Tang WW, Ekiz HA, Lane TE, Cluntun AA, Bettini ML, Round JL, Rutter J, O'Connell R (2020). Mitochondrial Pyruvate Carrier 1 Promotes Peripheral T Cell Homeostasis through Metabolic Regulation of Thymic Development. Cell reports, 30(9), 2889-2899.e6.
  26. 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, 3(2),
  27. Szwarc MM, Hai L, Maurya VK, Rajapakshe K, Perera D, Ittmann MM, Mo Q, Lin Y, Bettini ML, Coarfa C, Lydon J (2022). Histopathologic and transcriptomic phenotypes of a conditional RANKL transgenic mouse thymus. Cytokine, 160, 156022.
  28. 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.
  29. 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.
  30. 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.
  31. Raugh A, Jing Y, Bettini ML, Bettini (2023). The amphiregulin/EGFR axis has limited contribution in controlling autoimmune diabetes. Scientific reports, 13(1), 18653.

Review

  1. Bettini ML, Vignali DA (2010). Development of thymically derived natural regulatory T cells. [Review]. Ann N Y Acad Sci, 1183, 1-12.
  2. Bettini ML, Bettini, Vignali D (2012). T-cell receptor retrogenic mice: a rapid, flexible alternative to T-cell receptor transgenic mice. Immunology, 136(3), 265-72.
  3. Majumdar S, Lin Y, Bettini M (2022). Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes. Frontiers in immunology, 13, 974178.
  4. Reynolds HM, Bettini M (2023). Early-life microbiota-immune homeostasis. Frontiers in immunology, 14, 1266876.