Obesity accelerates T cell senescence in murine visceral adipose tissue

被引:200
|
作者
Shirakawa, Kohsuke [1 ]
Yan, Xiaoxiang [1 ,2 ]
Shinmura, Ken [3 ]
Endo, Jin [1 ]
Kataoka, Masaharu [1 ]
Katsumata, Yoshinori [1 ]
Yamamoto, Tsunehisa [1 ]
Anzai, Atsushi [1 ]
Isobe, Sarasa [1 ]
Yoshida, Naohiro [1 ,4 ]
Itoh, Hiroshi [5 ]
Manabe, Ichiro [6 ]
Sekai, Miho [7 ]
Hamazaki, Yoko [7 ]
Fukuda, Keiichi [1 ]
Minato, Nagahiro [7 ]
Sano, Motoaki [1 ,8 ]
机构
[1] Keio Univ, Sch Med, Dept Cardiol, Tokyo, Japan
[2] Shanghai Jiao Tong Univ, Sch Med, Dept Cardiol, Ruijin Hosp, Shanghai, Peoples R China
[3] Hyogo Coll Med, Dept Gen Med, Nishinomiya, Hyogo, Japan
[4] Tokyo Womens Med Univ, Dept Endocrinol & Hypertens, Tokyo, Japan
[5] Keio Univ, Sch Med, Dept Endocrinol Metab & Nephrol, Tokyo, Japan
[6] Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Tokyo, Japan
[7] Kyoto Univ, Grad Sch Med, Dept Immunol & Cell Biol, Kyoto, Japan
[8] Japan Sci & Technol JST Agcy, PREST, Tokyo, Japan
来源
JOURNAL OF CLINICAL INVESTIGATION | 2016年 / 126卷 / 12期
基金
日本学术振兴会;
关键词
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; INSULIN-RESISTANCE; OSTEOPONTIN; INFLAMMATION; MICE; EXPRESSION; DISEASE; MACROPHAGES; ACTIVATION; POPULATION;
D O I
10.1172/JCI88606
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Chronic inflammation in visceral adipose tissue (VAT) precipitates the development of cardiometabolic disorders. Although changes in T cell function associated with visceral obesity are thought to affect chronic VAT inflammation, the specific features of these changes remain elusive. Here, we have determined that a high-fat diet (HFD) caused a preferential increase and accumulation of CD44(hi)CD62L(lo)CD4(+) T cells that constitutively express PD-1 and CD153 in a B cell-dependent manner in VAT. These cells possessed characteristics of cellular senescence and showed a strong activation of Spp1 (encoding osteopontin [OPN]) in VAT. Upon T cell receptor stimulation, these T cells also produced large amounts of OPN in a PD-1resistant manner in vitro. The features of CD153(+)PD-1(+)CD44(hi)CD4(+) T cells were highly reminiscent of senescence-associated CD4(+) T cells that normally increase with age. Adoptive transfer of CD153(+)PD-1(+)CD44(hi)CD4(+) 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(+)PD1(+)CD44(hi)CD4(+) T cell population that accumulates in the VAT of HFD-fed obese mice causes VAT inflammation by producing large amounts of OPN. This finding suggests a link between visceral adiposity and immune aging.
引用
收藏
页码:4626 / 4639
页数:14
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