Lysosomal α-Galactosidase Controls the Generation of Self Lipid Antigens for Natural Killer T Cells
Copyright policy )Lysosomal α-Galactosidase Controls the Generation of Self Lipid Antigens for Natural Killer T Cells
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.
- Boston Children's Hospital United States
- National Institutes of Health United States
- Max Planck Society Germany
- Harvard University United States
- National Institute of Health Pakistan
Mice, Knockout, Antigen Presentation, Immunology, Toll-Like Receptors, Dendritic Cells, Lymphocyte Activation, Autoantigens, Lipids, Coculture Techniques, Mice, Inbred C57BL, Mice, Infectious Diseases, CELLIMMUNO, alpha-Galactosidase, Myeloid Differentiation Factor 88, Immunology and Allergy, Animals, Homeostasis, Natural Killer T-Cells, MOLIMMUNO, Lysosomes, Cells, Cultured, Signal Transduction
Mice, Knockout, Antigen Presentation, Immunology, Toll-Like Receptors, Dendritic Cells, Lymphocyte Activation, Autoantigens, Lipids, Coculture Techniques, Mice, Inbred C57BL, Mice, Infectious Diseases, CELLIMMUNO, alpha-Galactosidase, Myeloid Differentiation Factor 88, Immunology and Allergy, Animals, Homeostasis, Natural Killer T-Cells, MOLIMMUNO, Lysosomes, Cells, Cultured, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).111 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!