Diacylglycerol Lipase-β Is Required for TNF-α Response but Not CD8+ T Cell Priming Capacity of Dendritic Cells

被引:14
作者
Shin, Myungsun [1 ]
Buckner, Andrew [3 ]
Prince, Jessica [3 ]
Bullock, Timothy N. J. [3 ]
Hsu, Ku-Lung [1 ,2 ,4 ]
机构
[1] Univ Virginia, Dept Chem, McCormick Rd,POB 400319, Charlottesville, VA 22904 USA
[2] Univ Virginia, Sch Med, Dept Pharmacol, Charlottesville, VA 22908 USA
[3] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA
[4] Univ Virginia, Canc Ctr, Charlottesville, VA 22903 USA
来源
CELL CHEMICAL BIOLOGY | 2019年 / 26卷 / 07期
基金
美国国家卫生研究院;
关键词
CD70; EXPRESSION; IMMUNITY;
D O I
10.1016/j.chembiol.2019.04.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Diacylglycerol lipase-beta (DAGL beta) hydrolyzes arachidonic acid (AA)-esterified diacylglycerols to produce 2-arachidonoylglycerol (2-AG) and downstream prostanoids that mediate inflammatory responses of macrophages. Here, we utilized DAGL-tailored activity-based protein profiling and genetic disruption models to discover that DAGL beta regulates inflammatory lipid and protein signaling pathways in primary dendritic cells (DCs). DCs serve as an important link between innate and adaptive immune pathways by relaying innate signals and antigen to drive T cell clonal expansion and prime antigen-specific immunity. We discovered that disruption of DAGL beta in DCs lowers cellular 2-AG and AA that is accompanied by reductions in lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha secretion. Cell-based vaccination studies revealed that DC maturation ex vivo and immunogenicity in vivo was surprisingly unaffected by DAGL beta inactivation. Collectively, we identify DAGL beta pathways as a means for attenuating DC inflammatory signaling while sparing critical adaptive immune functions and further expand the utility of targeting lipid pathways for immunomodulation.
引用
收藏
页码:1036 / +
页数:9
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