Control of senescence-associated T cell-induction

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03925
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Kyoto University
• Principal Investigator: Hattori Masakazu 京都大学, 医学研究科, 特定教授 (40211479)
• Co-Investigator(Kenkyū-buntansha): 保富 康宏 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 霊長類医科学研究センター, センター長 (90281724) ; 福島 祐二 京都大学, 医学研究科, 特定助教 (90583146)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 免疫老化 / 老化関連T細胞 / CD153 / CD3複合体 / リバースシグナル / 加齢関連疾患 / オステオポンチン

Outline of Final Research Achievements

A memory-phenotype CD4+ T cells termed senescence-associated T (SA-T) cells are shown to be involved in the development of SLE and age-associated inflammatory diseases including Type 2 diabetes and chronic kidney diseases. The T cells steadily increase with age, but the mechanism on their increment in vivo remains elusive. In the present study, we found that CD153, which is constitutively expressed on SA-T cells, regulates their growth. CD153 was shown to bind to the CD3 complex on T cells, thereby inducing dissociation of T cell antigen receptor (TCR) alpha-beta with CD3 complex and inhibiting TCR signaling; A monoclonal antibody that completely block the interaction between CD153 and CD30 inhibited the increase in SA-T cells and the autoimmune response with age. The antibody could contribute to reducing SLE and the age-associated disorders such as chronic nephritis and Type 2 diabetes.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

高齢化社会において急増しつつある加齢関連疾患の制圧は現代社会の喫緊の課題であり，これに対する適切な医学定期対応は社会の強い要請となっている。加齢に伴い増加する老化関連T細胞は様々な加齢関連疾患の発症に関与しており，その制御の方法の一端を明らかにした今回の研究は，加齢関連疾患の予防および治療方法の創出に直接的に結びつく成果といえる。