Elucidation of molecular basis common to cardiovascular disorders associated with aging and metabolic syndrome

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04825
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Keio University
• Principal Investigator: SANO MOTOAKI 慶應義塾大学, 医学部(信濃町), 准教授 (30265798)
• Research Collaborator: SHIRAKAWA Kohsuke 慶應義塾大学, 医学部循環器内科研究室, 大学院生 ; YAMAMOTO Tsunehisa 慶應義塾大学, 医学部循環器内科研究室, 大学院生
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 免疫老化 / 肥満 / T細胞 / マクロファージ / 高脂肪食 / 内臓脂肪 / Ｂ細胞 / 養子免疫細胞移入

Outline of Final Research Achievements

Chronic inflammation in visceral adipose tissue (VAT) precipitates the development of cardiometabolic disorders. Here, we have determined that a high-fat diet (HFD) caused a preferential increase and accumulation of CD44hiCD62LloCD4+ T cells that constitutively express PD-1 and CD153 in VAT. These cells possessed characteristics of cellular senescence and produced large amounts of osteopontin (OPN) in a PD-1-resistant manner. The features of these T cells were highly reminiscent of senescence-associated CD4+ T cells that normally increase with age. Adoptive transfer of CD153+PD-1+CD44hiCD4+ T cells from HFD-fed WT, but not Spp1-deficient, mice into the VAT of lean mice fed a normal diet recapitulated the essential features of VAT inflammation and insulin resistance. Our results demonstrate that a distinct CD153+PD-1+CD44hiCD4+ T cell population causes VAT inflammation by producing large amounts of OPN. This finding suggests a link between visceral adiposity and immune aging.

Free Research Field

内科学、循環器、心臓