期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 120, 期 8, 页码 2889-2899出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI42703
关键词
-
资金
- NIH [DK-51362, DK-44319, DK-53056, HL-38180, DK-56260, DK-066917]
- Harvard Digestive Diseases Center
- Deutsche Forschungsgemeinschaft [Ze 814/1-1]
- Crohn's and Colitis Foundation of America
- Washington University Digestive Disease Center [DK-52574]
- Royal Society
- Medical Council
- Wellcome Trust [084923/B/08/7]
- MRC [G0400421, MC_U137884181] Funding Source: UKRI
- Cancer Research UK [11331] Funding Source: researchfish
- Medical Research Council [G0400421, MC_U137884181] Funding Source: researchfish
Abetalipoproteinemia (ABL) is a rare Mendelian disorder of lipid metabolism due to genetic deficiency in microsomal triglyceride transfer protein (MTP). It is associated with defects in MTP-mediated lipid transfer onto apolipoprotein B (APOB) and impaired secretion of APOB-containing lipoproteins. Recently, MTP was shown to regulate the CD1 family of lipid antigen-presenting molecules, but little is known about immune function in ABL patients. Here, we have shown that ABL is characterized by immune defects affecting presentation of self and microbial lipid antigens by group 1 (CD la, CD1b, CD1c) and group 2 (CD1d) CD1 molecules. In dendritic cells isolated from ABL patients, MTP deficiency was associated with increased proteasomal degradation of group 1 CD1 molecules. Although CD1d escaped degradation, it was unable to load antigens and exhibited functional defects similar to those affecting the group 1 CD1 molecules. The reduction in CD1 function resulted in impaired activation of CD1-restricted T and invariant natural killer T (iNKT) cells and reduced numbers and phenotypic alterations of iNKT cells consistent with central and peripheral CD1 defects in vivo. These data highlight MTP as a unique regulator of human metabolic and immune pathways and reveal that ABL is not only a disorder of lipid metabolism but also an immune disease involving CD1.
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