Bull’s-eye: Targeted Immune Treatments for Diabetes
T1D is an autoimmune disease where effector T cells (Teff) attack the islet cells that produce insulin. This autoreactivity continues because of dysfunctional regulatory T cells (Treg) that normally function to suppress the Teff cells. Recently, therapeutic strategies have been aimed at targeting T cells for T1D treatment and prevention.
All the RAGE
RAGE is a receptor implicated with inflammatory disease and expressed in various cells in T1D, including T cells. One study suggested short-term treatment of sRAGE (an antagonist competing for RAGE ligands) in mouse models and human Tregs as a prospective preventative therapy for T1D due to various findings:
- Decreased islet infiltration
- Increased ratios of Tregs to Teffs in the pancreatic lymph nodes and spleen
- Accelerated proliferation of human natural Tregs
- Improved oral glucose tolerance and insulin expression
- Reduced risk of T1D
Engineered T cells
Researchers from Seattle Children’s and Benaroya research institutes designed a strategy using HDR (homology-directed repair)-based gene editing to induce FOXP3 expression, creating edited Treg cells:edTregs. They found that the antigen-specific edTregs acted like regular Tregs with functional FOXP3 expression, offering protective and immunosuppressive effects. According to Dr. David Rawlings, this therapy could theoretically be used to suppress the immune response by injecting a patient’s own genetically engineered T cells into their pancreas, protecting islet function. He and fellow researchers hope to create a long-term immunological “tolerance,” creating a therapy that could last years or even be a cure for patients with newly developing T1D.
What’s next: T cells have an important role in the context of T1D, and more research is required in T cells from both healthy and diabetic models to understand therapeutic approaches. sRAGE shows promise as a prevention, but more knowledge about the role of RAGE is needed. After research advances in a clinical direction, edTreg could lead to universal Treg therapies in the long-term.
- Leung, S. S., Borg, D. J., Mccarthy, D. A., Boursalian, T. E., Cracraft, J., Zhuang, A., . . . Forbes, J. M. (2020). Expansion of Functional Regulatory T Cells Using Soluble RAGE Prevents Type 1 Diabetes. doi:10.1101/2020.01.10.902627
- Honaker, Y., Hubbard, N., Xiang, Y., Fisher, L., Hagin, D., Sommer, K., . . . Rawlings, D. J. (2020). Gene editing to induce FOXP3 expression in human CD4+ T cells leads to a stable regulatory phenotype and function. Science Translational Medicine, 12(546). doi:10.1126/scitranslmed.aay6422
- Staff, S. (2020, June 03). Engineered T cells for type 1 diabetes move closer to clinic. Retrieved July 22, 2020, from https://medicalxpress.com/news/2020-06-cells-diabetes-closer-clinic.html
- Henderson, E. (2020, June 22). Developments in Engineered T Cells for Type 1 Diabetes. Retrieved July 22, 2020, from https://www.azolifesciences.com/news/20200623/Developments-in-Engineered-T-Cells-for-Type-1-Diabetes.aspx