期刊
JCI INSIGHT
卷 5, 期 16, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.138034
关键词
-
资金
- UAB Department of CDIB
- Stavros Niarchos Foundation
- JDRF [3-PDF2017-385-A-N]
- Veteran's Administration [BX001792, 13F-RCS-002]
- NIH [R01DK-69455, R01 DK110292, R01 HL125353, U01 HD087198, RR031535, R01 AI139072, R01 DK074656]
- USF [0131845]
Type 1 diabetes (T1D) is a consequence of autoimmune beta cell destruction, but the role of lipids in this process is unknown. We previously reported that activation of Ca2+-independent phospholipase A2 beta (iPLA2 beta) modulates polarization of macrophages (MG.). Hydrolysis of the sn-2 substituent of glycerophospholipids by iPLA2 beta can lead to the generation of oxidized lipids (eicosanoids), pro-and antiinflammatory, which can initiate and amplify immune responses triggering beta cell death. As MG. are early triggers of immune responses in islets, we examined the impact of iPLA2 beta-derived lipids (iDLs) in spontaneous-T1D prone nonobese diabetic mice (NOD), in the context of MG. production and plasma abundances of eicosanoids and sphingolipids. We find that (a) MG.NOD exhibit a proinflammatory lipid landscape during the prediabetic phase; (b) early inhibition or genetic reduction of iPLA2 beta reduces production of select proinflammatory lipids, promotes antiinflammatory MG. phenotype, and reduces T1D incidence; (c) such lipid changes are reflected in NOD plasma during the prediabetic phase and at T1D onset; and (d) importantly, similar lipid signatures are evidenced in plasma of human subjects at high risk for developing T1D. These findings suggest that iDLs contribute to T1D onset and identify select lipids that could be targeted for therapeutics and, in conjunction with autoantibodies, serve as early biomarkers of pre-T1D.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据