JEM: Targeting special T-cell proteins may inhibit the development of type 1 diabetes

DECEMBER 14, 2020 // -- In a recent study published in the international journal Journal of Laboratory Medicine, scientists from the University of Utah School of Medicine and others identified a new therapeutic target or could help treat type 1 diabetes patients by inhibiting a protein called OCA-B or protecting mice from the activity of β cells that destroy insulin-producing cells in the pancreas.
picture source: 2020 Kim et al. Originally published in Journal of Experimental Medicine. doi:10.1084/jem.202005331 type diabetes is an autoimmune disease in which the patient's immune system mistakenly attacks pancreatic β cells, thereby cutting off insulin production, and patients usually need insulin therapy for life to maintain the body's proper blood sugar levels, and there is currently no therapy to prevent the immune system from attacking β
T cells are able to identify specific molecules produced by invading bacteria and viruses, and when T cells encounter these molecules called antigens, they turn on the expression of hundreds of genes to fight infection, and a special protein called OCA-B binds to many of them and helps ensure that T cells are more easily reactivated the next time they encounter the same antigen.
In many autoimmune diseases, T-cells mistakenly identify and respond to antigens produced by normal healthy cells, and repeated antigen exposure may be a common property of autoimmune responses, the researchers hypothesized that the targeting protein OCA-B may inhibit autologic, diabetic T-cell responses.
study, researcher Tantin and colleagues found that mice prone to type 1 diabetes were protected from the disease if they lacked OCA-B protein.
Potential autoreactive cytotoxic T cells (which can directly target and kill pancreas β cells) remain inactive and do not accumulate in the pancreas, while potential autologic reactive auxiliary T cells (which recruit other immune cells to induce destructive inflammatory reactions) accumulate in the pancreas and remain unresponsive.
researchers say OCA-B can chemically modify the activity of T cells by recruiting enzymes called Jmjd1a to chemically modify the DNA of the surrounding chromosomes, and researcher Tantin and colleagues designed a small peptide that inhibits OCA-B. The association with Jmjd1a, and preventing the reactivation of ionization T cells in the laboratory, injecting the peptide into prediabetes mice reduced the activity of the reactive T cells in the body, reduced inflammation of the pancreas and restored blood sugar levels to normal.
Final researcher Tantin said that while the peptide is currently unlikely to be used in clinical studies, it may provide principled evidence that OCA-B protein is a therapeutic target for type 1 diabetes and could be used as a new tool in the future to help develop new treatments for type 1 diabetes.
() Original source: Heejoo Kim, Jelena Perovanovic, Arvind Shakya, et al. Targeting transcriptional coregulator OCA-B/Pou2af1 blocks activated autoreactive T cells in the pancreas and type 1 diabetes, Journal of Experimental Medicine (2020) doi:10.1084/jem.20200533。