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Matthew L. Bettini

Matthew L. Bettini, PhD

Languages spoken: English

Academic Information

Departments Primary - Pathology

Academic Office Information

Research Interests

  • T Cell Development
  • Tolerance to Microbiota
  • Chimeric Antigen Receptor (CAR) Signaling in Function and Persistence
  • Autoimmunity

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

Research Fellow St. Jude Children's Research Hospital
Postdoctoral Research Fellow
Emory University
Graduate Training Georgia State University
Furman University

Selected Publications

Journal Article

  1. Szwarc MM, Hai L, Maurya VK, Rajapakshe K, Perera D, Ittmann MM, Mo Q, Lin Y, Bettini ML, Coarfa C, Lydon JP (2022). Histopathologic and transcriptomic phenotypes of a conditional RANKL transgenic mouse thymus. Cytokine, 160, 156022.
  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. 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 GE (2021). Thymic development of gut-microbiota-specific T cells. Nature, 594(7863), 413-417.
  6. Bettini M, Bettini ML (2021). Function, Failure, and the Future Potential of Tregs in Type 1 Diabetes. Diabetes, 70(6), 1211-1219.
  7. Ramstead AG, Wallace JA, Lee SH, Bauer KM, Tang WW, Ekiz HA, Lane TE, Cluntun AA, Bettini ML, Round JL, Rutter J, OConnell RM (2018). Mitochondrial Pyruvate Carrier 1 Promotes Peripheral T Cell Homeostasis through Metabolic Regulation of Thymic Development. Cell Rep, 30(9), 2889-2899.e6.
  8. 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.
  9. Shrestha AK, Bettini ML, Menon RT, Gopal VYN, Huang S, Edwards DP, Pammi M, Barrios R, Shivanna B (2019). Consequences of early postnatal lipopolysaccharide exposure on developing lungs in mice. Am J Physiol Lung Cell Mol Physiol, 316(1), L229-L244.
  10. Kim M, Galan C, Hill AA, Wu WJ, Fehlner-Peach H, Song HW, Schady D, Bettini ML, Simpson KW, Longman RS, Littman DR, Diehl GE (2018). Critical Role for the Microbiota in CX3CR1+ Intestinal Mononuclear Phagocyte Regulation of Intestinal T Cell Responses. Immunity, 49(1), 151-163.e5.
  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, 200(3), 909-914.
  12. Bettini ML, Bettini M (2017). Understanding Autoimmune Diabetes through the Prism of the Tri-Molecular Complex. Front Endocrinol (Lausanne), 8, 351.
  13. Lee T, Sprouse ML, Banerjee P, Bettini, 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. Bettini ML, Chou PC, Guy CS, Lee T, Vignali KM, Vignali DAA (2017 Sep 1). Cutting Edge: CD3 ITAM Diversity Is Required for Optimal TCR Signaling and Thymocyte Development. J Immunol, 199(5), 1555-1560.
  15. Bettini ML, Guy C, Dash P, Vignali KM, Hamm DE, Dobbins J, Gagnon E, Thomas PG, Wucherpfennig KW, Vignali DA (2014). Membrane association of the CD3epsilon signaling domain is required for optimal T cell development and function. J Immunol, 193(1), 258-67.
  16. Bettini ML, Bettini, 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.
  17. Bettini ML, Pan F, Bettini M, Finkelstein D, Rehg JE, Floess S, Bell BD, Ziegler SF, Huehn J, Pardoll DM, Vignali DA (2012 May 25). Loss of epigenetic modification driven by the Foxp3 transcription factor leads to regulatory T cell insufficiency. Immunity, 36(5), 717-30.


  1. Majumdar S, Lin Y, Bettini ML (2022). Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes. [Review]. Front Immunol, 13, 974178.
  2. Bettini ML, Bettini, Vignali DA (2012). T-cell receptor retrogenic mice: a rapid, flexible alternative to T-cell receptor transgenic mice. [Review]. Immunology, 136(3), 265-72.

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