Therapeutic strategies to inhibit the progression of type 1 diabetes mellitus by focusing on the differentiation of CD8-positive T cells.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20934
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0904:Internal medicine of the bio-information integration and related fields
• Research Institution: Kyushu University
• Principal Investigator: Miyachi Yasutaka 九州大学, 大学病院, 助教 (00801515)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 1型糖尿病 / FoxO1 / CD8陽性T細胞

Outline of Final Research Achievements

Type 1 diabetes is an autoimmune disease characterized by insulitis and CD8-positive T cells are the most common inflammatory cells in insulitis. FoxO1 is a transcription factor that is important for T cell differentiation.
We confirmed that stimulation of CD8-positive T cells with FoxO1 inhibitors decreased IFNg production and secretion.
Administration of FoxO1 inhibitors to NOD mice did not affect blood glucose levels or body weight. Analysis of pancreatic tissue sections showed that FoxO1 inhibitors caused no apparent difference in the infiltration of T cells, including CD8 T cells, into the islets compared to controls.

Free Research Field

内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

転写因子FoxO1がCD8T細胞の分化に加えて、IFNg産生と分泌に関与することが明らかとなった。一方で、1型糖尿病の病態にFoxO1がどの程度関与するかについては、今回は前糖尿病状態の個体に薬剤を投与したため、まだ結論がでていない。今後は、糖尿病発症直前あるいは発症後の個体への薬剤投与を行い検証をすすめる予定である。