Study on the mechanism(s) of immunosenescence and its application for vaccine development.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26450443
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Integrative animal 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(Renkei-kenkyūsha): MASHIMO Tomoji 大阪大学, 大学院医学研究科, 准教授 (80397554)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 免疫老化 / T細胞 / PD-1 / CD153 / オステオポンチン / 全身性エリテマトーデス / 死細胞処理 / 貪食

Outline of Final Research Achievements

Immune aging results in diminished adaptive immunity and increased risk for autoimmunity. We previously discovered a unique T cell population that increases with age, termed senescence-associated (SA-) T cells. The SA-T cells secret abundant osteopontin (OPN) in respond to auto B cells. Here, we demonstrate that OPN secreted by SA-T cells, which selectively accumulate in the germinal centers (GCs) of lupus-prone mice, interferes with phagocytosis of apoptotic cells. OPN induced diffuse and prolonged Rac1 activation in phagocytes via integrin alpha v beta 3 and inhibited the dissolution of phagocytic actin cup, causing defective apoptotic cell engulfment. Our results suggest that OPN secreted by follicular SA-T cells in GCs promotes a continuous supply of intracellular autoantigens via apoptotic cells, thus playing a key role in the progression of the autoreactive GC reaction and leading to pathogenic autoantibody production in lupus-prone mice.

Free Research Field

免疫学