Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes

被引：253

作者：

Thompson, Peter J. ^{[1
]}

Shah, Ajit ^{[1
]}

Ntranos, Vasilis ^{[2
,3
]}

Van Gool, Frederic ^{[1
]}

Atkinson, Mark ^{[4
]}

Bhushan, Anil ^{[1
]}

机构：

[1] Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94143 USA

[2] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA

[3] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA

[4] Univ Florida, Diabet Inst, Gainesville, FL 32610 USA

来源：

CELL METABOLISM | 2019年 / 29卷 / 05期

关键词：

CELLULAR SENESCENCE; SECRETORY PHENOTYPE; TECHNOLOGIES; SURVEILLANCE; PROGRESSION; INHIBITION; CLEARANCE; REVEALS; DISEASE; DEVELOP;

D O I：

10.1016/j.cmet.2019.01.021

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Type 1 diabetes (T1D) is an organ-specific autoimmune disease characterized by hyperglycemia due to progressive loss of pancreatic beta cells. Immune-mediated beta cell destruction drives the disease, but whether beta cells actively participate in the pathogenesis remains unclear. Here, we show that during the natural history of T1D in humans and the non-obese diabetic (NOD) mouse model, a subset of beta cells acquires a senescence-associated secretory phenotype (SASP). Senescent beta cells upregulated pro-survival mediator Bcl-2, and treatment of NOD mice with Bcl-2 inhibitors selectively eliminated these cells without altering the abundance of the immune cell types involved in the disease. Significantly, elimination of senescent beta cells halted immune-mediated beta cell destruction and was sufficient to prevent diabetes. Our findings demonstrate that beta cell senescence is a significant component of the pathogenesis of T1D and indicate that clearance of senescent beta cells could be a new therapeutic approach for T1D.

引用

页码：1045 / +

页数：26

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