Cutting edge: Impaired glycosphingolipid trafficking and NKT cell development in mice lacking Niemann-Pick type C1 protein
Cutting edge: Impaired glycosphingolipid trafficking and NKT cell development in mice lacking Niemann-Pick type C1 protein
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DOI：
10.4049/jimmunol.177.1.26
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发表时间：
2006-07-01
影响因子：
4.4
通讯作者：
Bendelac, Albert
中科院分区：
文献类型：
--
作者：
Sagiv, Yuval;Hudspeth, Kelly;Bendelac, Albert
Niemann-Pick Type C1 (NPC1) is a late endosomal/lysosomal transmembrane protein involved in the cellular transport of glycosphingolipids and cholesterol that is mutated in a majority of patients with Niemann-Pick C neurodegenerative disease. We found that NPC1-deficient mice lacked V alpha 14-J alpha 18 NKT cells, a major population of CD1d-restricted T cells that is conserved in humans. NPC1-deficient mice also exhibited marked defects in the presentation of Sphingomonas cell wall Ags to NKT cells and in bacterial clearance in vivo. A synthetic fluorescent alpha-glycosylceramide analog of the Sphingomonas Ag trafficked to the lysosome of wild-type cells but accumulated in the late endosome of NPC1-deficient cells. These findings reveal a blockade of lipid trafficking between endosome and lysosome as a consequence of NPC1 deficiency and suggest a common mechanism for the defects in lipid presentation and development of Va14-Ja18 NKT cells.
