id:"swepub:oai:gup.ub.gu.se/132315"
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- Darmoise, Alexandre (author)
Lysosomal alpha-galactosidase controls the generation of self lipid antigens for natural killer T cells.
- Article/chapterEnglish2010
Publisher, publication year, extent ...
- Elsevier BV,2010
Numbers
- LIBRIS-ID:oai:gup.ub.gu.se/132315
- https://gup.ub.gu.se/publication/132315URI
- https://doi.org/10.1016/j.immuni.2010.08.003DOI
Supplementary language notes
- Language:English
Part of subdatabase
- SwePubSwePub
Classification
Notes
- Natural Killer T (NKT) cells are lipid-reactive, CD1d-restricted T lymphocytes important in infection, cancer, and autoimmunity. In addition to foreign antigens, NKT cells react with endogenous self lipids. However, in the face of stimulating self antigen, it remains unclear how overstimulation of NKT cells is avoided. We hypothesized that constantly degraded endogenous antigen only accumulates upon inhibition of alpha-galactosidase A (alpha-Gal-A) in lysosomes. Here, we show that alpha-Gal-A deficiency caused vigorous activation of NKT cells. Moreover, microbes induced inhibition of alpha-Gal-A activity in antigen-presenting cells. This temporary enzyme block depended on Toll-like receptor (TLR) signaling and ultimately triggered lysosomal lipid accumulation. Thus, we present TLR-dependent negative regulation of alpha-Gal-A as a mechanistic link between pathogen recognition and self lipid antigen induction for NKT cells.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Andra medicinska och farmaceutiska grundvetenskaper hsv//swe
- MEDICAL AND HEALTH SCIENCES Basic Medicine Other Basic Medicine hsv//eng
- Animals
- Antigen Presentation
- Autoantigens
- immunology
- Cells
- Cultured
- Coculture Techniques
- Dendritic Cells
- immunology
- Homeostasis
- Lipids
- immunology
- Lymphocyte Activation
- Lysosomes
- enzymology
- immunology
- Mice
- Mice
- Inbred C57BL
- Mice
- Knockout
- Myeloid Differentiation Factor 88
- deficiency
- immunology
- metabolism
- Natural Killer T-Cells
- enzymology
- immunology
- Signal Transduction
- Toll-Like Receptors
- immunology
- metabolism
- alpha-Galactosidase
- immunology
- metabolism
Added entries (persons, corporate bodies, meetings, titles ...)
- Teneberg, Susann,1955Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology(Swepub:gu)xtensu (author)
- Bouzonville, Lauriane (author)
- Brady, Roscoe O (author)
- Beck, Michael (author)
- Kaufmann, Stefan H E (author)
- Winau, Florian (author)
- Göteborgs universitetInstitutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi (creator_code:org_t)
Related titles
- In:Immunity: Elsevier BV33:2, s. 216-281097-41801074-7613
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