Cutting edge: Impaired glycosphingolipid trafficking and NKT cell development in mice lacking Niemann-Pick Type C1 protein

Yuval Sagiv, Kelly Hudspeth, Jochen Mattner, Nicolas Schrantz, Randi K. Stern, Dapeng Zhou, Paul B. Savage, Luc Teyton, Albert Bendelac

Research output: Contribution to journalArticle

Abstract

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 Vα14-Jα18 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 α-glycosylceramide analog of the Sphingomonas Ag trafficked to the lysosome of wild-type cells but accumulated in the late endosome of NPC1-deficient ceils. 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 Vα14-Jα18 NKT cells.

Original languageEnglish
Pages (from-to)26-30
Number of pages5
JournalJournal of Immunology
Volume177
Issue number1
Publication statusPublished - Jul 1 2006

ASJC Scopus subject areas

  • Immunology

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    Sagiv, Y., Hudspeth, K., Mattner, J., Schrantz, N., Stern, R. K., Zhou, D., Savage, P. B., Teyton, L., & Bendelac, A. (2006). Cutting edge: Impaired glycosphingolipid trafficking and NKT cell development in mice lacking Niemann-Pick Type C1 protein. Journal of Immunology, 177(1), 26-30.