Invariant natural killer T cells are phenotypically and functionally altered in Fabry disease

Pereira, Cátia; Azevedo, Olga; Maia, Maria Luz; Dias, Ana Cristina; Sá-Miranda, C; Macedo, Mário

doi:10.1016/j.ymgme.2013.01.018

Cited by 37 publications

(41 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the possibility that small amounts of α-linked glycosylceramides could be produced by these enzymes or that under certain physiologic conditions, such as the acidic environment of the lysosome, α-linked species could be produced with the help of anomerases will have to be examined; we already know that the prolonged exposure of α-GalCer and psychosine to pH 4.0 did not lead to any measurable conversion to α-anomers (Figure S4). The role that catabolism might play in the availability of endogenous NKT ligands was suggested by the phenotype of NKT cells in α-galactosidase (GLA) deficiency, also known as Fabry disease, in mice and humans (Darmoise et al, 2010; Pereira et al, 2013). Indeed, the absence of GLA resulted in a profile of NKT cell hyperstimulation that correlated with the presence of an increased amount of self-ligands at the surface of selecting thymocytes and peripheral antigen-presenting cells (Darmoise et al, 2010; Pereira et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

“…The role that catabolism might play in the availability of endogenous NKT ligands was suggested by the phenotype of NKT cells in α-galactosidase (GLA) deficiency, also known as Fabry disease, in mice and humans (Darmoise et al, 2010; Pereira et al, 2013). Indeed, the absence of GLA resulted in a profile of NKT cell hyperstimulation that correlated with the presence of an increased amount of self-ligands at the surface of selecting thymocytes and peripheral antigen-presenting cells (Darmoise et al, 2010; Pereira et al, 2013). We confirmed that compared to DCs from littermate control animals, GLA-deficient DCs were hyperstimulatory toward DN32.D3 T cells and that this activity was inhibited by L363 antibody (data not shown).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The Identification of the Endogenous Ligands of Natural Killer T Cells Reveals the Presence of Mammalian α-Linked Glycosylceramides

et al. 2014

View full text Add to dashboard Cite

Summary Glycosylceramides in mammalian species are thought to be present in the form of β-anomers. This conclusion was reinforced by the identification of only one glucosylceramide and one galactosylcerhamide synthase, both β-transferases, in mammalian genomes. Thus, the possibility that small amounts of α-anomers could be produced by an alternative enzymatic pathway, by an unfaithful enzyme, or spontaneously in unusual cellular compartments has not been examined in detail. We approached the question by taking advantage of the exquisite specificity of T and B lymphocytes and combined it with the specificity of catabolic enzymes of the sphingolipid pathway. Here, we demonstrate that mammalian immune cells produce constitutively very small quantities of α-glycosylceramides, which are the major endogenous ligands of natural killer T cells. Catabolic enzymes of the ceramide and glycolipid pathway tightly control the amount of these α-glycosylceramides. The exploitation of this pathway to manipulate the immune response will create new therapeutic opportunities.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The Identification of the Endogenous Ligands of Natural Killer T Cells Reveals the Presence of Mammalian α-Linked Glycosylceramides

et al. 2014

View full text Add to dashboard Cite

show abstract

“…This absence of disorder in iNKTs has been thought to result from the differences in intracellular trafficking of mouse and human CD1d molecules or the role of ERT. More recently, Pereira et al reported a decrease in CD4 iNKTs, an increase of DN iNKTs and a reduction in the IL-4 production, without significant difference between ERT-treated and untreated patients (Pereira et al 2013). Of note, only 4 patients were treated among the 15 included, limiting the impact of ERT.…”

Section: Introductionmentioning

confidence: 99%

“…As previously mentioned, ERT could have a beneficial impact on innate immune response in FD in terms of iNKT cell counts (Macedo et al 2012;Pereira et al 2013). But no dedicated prospective and controlled study has been done to evaluate the impact of ERT on innate immune response as an endpoint in human.…”

Section: Introductionmentioning

confidence: 99%

Innate and Adaptive Immune Response in Fabry Disease

et al. 2015

View full text Add to dashboard Cite

Fabry disease is an X-linked lysosomal storage disease in which mutations of the gene (GLA) cause a deficiency of the lysosomal hydrolase α-galactosidase A (α-Gal). This defect results in an accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3) which causes a multisystemic vasculopathy. Available since 2001 in Europe, enzyme replacement therapy consists in the administration of agalsidase, a recombinant form of α-galactosidase A. Enzyme replacement therapy was shown to improve the global prognosis but allowed partial success in preventing critical events such as strokes and cardiac arrests. As in most lysosomal storage diseases, frequent immune reactions have been described in naive Fabry disease patients. Humoral immune responses following enzyme replacement therapy have also been described, with unclear consequences on the progression of the disease. While cost-effectiveness of enzyme replacement therapy in Fabry disease begins to be questioned and new therapeutic strategies arise such as chaperone or gene therapy, it appears necessary to better understand the immune responses observed in the treatment of naive patients and during enzyme replacement therapy with agalsidase. We propose a comprehensive review of the available literature concerning both innate and adaptive responses observed in Fabry disease. We particularly highlight the probable role of the toll-like receptor 4 (TLR4) and CD1d pathways triggered by Gb3 accumulation in the development of local and systemic inflammation that could lead to irreversible organ damages. We propose an immunological point of view of Fabry disease pathogenesis involving immune cells notably the invariant natural killer T cells. We finally review anti-agalsidase antibodies, their development and impact on outcomes.

show abstract

“…It is therefore necessary to analyze the different iNKT cell subsets in pathology, since their impact in disease may be different. Indeed, alterations in iNKT cell CD4+/CD4− subsets were described in Fabry disease, a lysosomal storage disease characterized by accumulation of glycosphingolipids, despite the fact that a normal percentage of total iNKT cells was observed in the peripheral blood of patients [109–111]. …”

Section: Cd1-restricted T Cellsmentioning

confidence: 99%

CD1-Restricted T Cells at the Crossroad of Innate and Adaptive Immunity

Pereira

Macedo

2016

Journal of Immunology Research

Self Cite

View full text Add to dashboard Cite

Lipid-specific T cells comprise a group of T cells that recognize lipids bound to the MHC class I-like CD1 molecules. There are four isoforms of CD1 that are expressed at the surface of antigen presenting cells and therefore capable of presenting lipid antigens: CD1a, CD1b, CD1c, and CD1d. Each one of these isoforms has distinct structural features and cellular localizations, which promotes binding to a broad range of different types of lipids. Lipid antigens originate from either self-tissues or foreign sources, such as bacteria, fungus, or plants and their recognition by CD1-restricted T cells has important implications in infection but also in cancer and autoimmunity. In this review, we describe the characteristics of CD1 molecules and CD1-restricted lipid-specific T cells, highlighting the innate-like and adaptive-like features of different CD1-restricted T cell subtypes.

show abstract

Invariant natural killer T cells are phenotypically and functionally altered in Fabry disease

Cited by 37 publications

References 29 publications

The Identification of the Endogenous Ligands of Natural Killer T Cells Reveals the Presence of Mammalian α-Linked Glycosylceramides

The Identification of the Endogenous Ligands of Natural Killer T Cells Reveals the Presence of Mammalian α-Linked Glycosylceramides

Innate and Adaptive Immune Response in Fabry Disease

CD1-Restricted T Cells at the Crossroad of Innate and Adaptive Immunity

Contact Info

Product

Resources

About