Matthew L. Bettini

Matthew L. Bettini, PhD, MS

Languages spoken: English

Academic Information

Departments Primary - Pathology

Lab

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
Doctoral Training Emory University
 PhD
Graduate Training Georgia State University
 MS
Undergraduate Furman 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. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Bettini M, Bettini ML (2021). Function, Failure, and the Future Potential of Tregs in Type 1 Diabetes. Diabetes, 70(6), 1211-1219.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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, 3(2).
  14. Bettini ML, Bettini M (2017). Understanding Autoimmune Diabetes through the Prism of the Tri-Molecular Complex. Front Endocrinol (Lausanne), 8, 351.
  15. 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.
  16. 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.
  17. 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. J Immunol Methods, 439, 29-36.
  18. Lee T, Shevchenko I, Sprouse ML, Bettini, Bettini ML (2016 Jul 11). Retroviral Transduction of Bone Marrow Progenitor Cells to Generate T-cell Receptor Retrogenic Mice.LID - 10.3791/54196 [doi]. J Vis Exp, (113).
  19. Paust S, Bettini M (2015). Daring to learn from humanized mice. Blood, 125(25), 3829-31.
  20. 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.
  21. 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.
  22. Delgoffe GM, Woo SR, Turnis ME, Gravano DM, Guy C, Overacre AE, Bettini ML, Vogel P, Finkelstein D, Bonnevier J, Workman CJ, Vignali DA (2013). Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis. Nature, 501(7466), 252-6.
  23. 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 DA (2013). Distinct TCR signaling pathways drive proliferation and cytokine production in T cells. Nat Immunol, 14(3), 262-70.
  24. Delgoffe GM, Bettini ML, Vignali DA (2012 Nov 16). Identity crisis: it's not just Foxp3 anymore. Immunity, 37(5), 759-61.
  25. 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.
  26. 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.
  27. 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 DA (2010 Apr 7). Tonic ubiquitylation controls T-cell receptor:CD3 complex expression during T-cell development. EMBO J, 29(7), 1285-98.
  28. Bettini ML, Kersh GJ (2007 Oct 9). MAP kinase phosphatase activity sets the threshold for thymocyte positive selection. Proc Natl Acad Sci U S A, 104(41), 16257-62.
  29. Kucharzik T, Hudson JT 3rd, Lugering A, Abbas JA, Bettini M, Lake JG, Evans ME, Ziegler TR, Merlin D, Madara JL, Williams IR (2005 Nov). Acute induction of human IL-8 production by intestinal epithelium triggers neutrophil infiltration without mucosal injury. Gut, 54(11), 1565-72.
  30. Bettini M, Xi H, Kersh GJ (2003 Nov). T cell stimulation in the absence of exogenous antigen: a T cell signal is induced by both MHC-dependent and -independent mechanisms. Eur J Immunol, 33(11), 3109-16.
  31. Bettini M, Xi H, Milbrandt J, Kersh GJ (2002 Aug 15). Thymocyte development in early growth response gene 1-deficient mice. J Immunol, 169(4), 1713-20.

Review

  1. Reynolds HM, Bettini ML (2023). Early-life microbiota-immune homeostasis. [Review]. Front Immunol, 14, 1266876.
  2. 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.
  3. 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.
  4. Bettini ML, Vignali DA (2010). Development of thymically derived natural regulatory T cells. [Review]. Ann N Y Acad Sci, 1183, 1-12.