Development of immunotherapy for type 1 diabetes

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22776
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Kyoto University
• Principal Investigator: Yano Hisashi 京都大学, iPS細胞研究所, 研究員 (80880749)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 制御性T細胞 / iPS細胞 / 自己免疫疾患 / GvHD

Outline of Final Research Achievements

For autoimmune diseases and graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation, treatments that weaken the entire immune system are used, resulting in many side effects. If regulatory T cells (Tregs) specific to the causative antigen could be transplanted, it could become a curative therapy. However, primary Tregs are difficult to proliferate, and practical application remains out of reach. Therefore, I aimed to establish a method to convert T cells, which were re-differentiated from iPS cells, into Tregs. I screened and identified a combination of drugs that induce the expression of FOXP3, a protein that characterizes Tregs, in iPSC-derived T cells. Furthermore, we confirmed that iPSC-derived T cells, with induced FOXP3 expression, suppressed the proliferation of cytotoxic T cells in vitro and inhibited GvHD in mice in vivo.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

自己免疫疾患や移植片対宿主病に対しては根治療法が存在せず、免疫全体を抑制する治療が行われているため、易感染性など副作用も多い。原因抗原特異的なTregの治療応用は以前からのアイデアであるが、その増殖のしにくさから実用化できていなかった。旺盛な増殖能を持つiPS細胞由来T細胞をTreg様細胞に転換することに成功した本研究成果は、自己免疫疾患の原因療法の確立に道を開くものである。また、Tregへの転換作用のある薬剤の検索・同定の過程で得られた遺伝子発現や細胞の機能変化に関するデータは、Tregの分化機序や機能の解明に資するものであり、発生生物学にも貢献を果たしたと言うことができる。