The role of Fas ligand in immune privilege

La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Nature Reviews Molecular Cell Biology (Impact Factor: 37.81). 01/2002; 2(12):917-24. DOI: 10.1038/35103104
Source: PubMed


Immune privilege is a property of some sites in the body, whereby immune responses are limited or prevented. One explanation that has been proposed for this phenomenon is engagement of the pro-apoptotic molecule Fas by its ligand (FasL), which leads to apoptosis, and consequently limits an inflammatory response. This idea has recently been challenged, and here we review the evidence for and against a role for FasL in immune privilege.

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    • "However, it is now known that FasL is present in many other cell types in various Disease Markers organs, such as the brain, eyes, placenta and testicles. This protein has been associated with the mechanism of " immune privilege, " protecting the organs from inflammation through the activation of apoptosis [7] [8]. Furthermore, this ligand is a major mediator of the cytolytic action of CD8+ T lymphocytes and natural killer cells [9]. "
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    ABSTRACT: Objective: This study investigated the association of the single nucleotide polymorphisms (SNPs) in the FAS and FASL genes with the outcome of hepatitis B virus (HBV) infection. Methods: Blood samples were collected from 116 HBV-infected patients at the Hospital of the Santa Casa de Misericordia Foundation (Belém, PA, Brazil). Seronegative individuals were used as controls. DNA samples were extracted from the leukocytes and assayed using the polymerase chain reaction (PCR) followed by RFLP analysis with restriction endonucleases. Results: The frequencies of the mutant genotypes for -670FAS (GG), Ivs2nt-124FASL (GG), Ivs3nt-169FASL (ΔT/ΔT), and -844FASL (TT) were higher in the HBV patients, and the FAS-1377AA genotype was more frequent in the control group; however, the differences between the allele and genotype frequencies were not statistically significant. When the HBV patient population was divided into two groups (inactive carriers and active chronic hepatitis patients), the mutant genotypes were found to be more prevalent in the active chronic hepatitis group with respect to the FAS gene polymorphisms; however, this difference was not statistically significant. Conclusions: The results suggest that the polymorphisms in FAS and FASL genes are not associated with HBV infection or even with the natural history of the infection in the Brazilian Amazon region.
    Disease markers 11/2013; 35(6):741-746. DOI:10.1155/2013/964145 · 1.56 Impact Factor
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    • "CD95L is a natural immunosuppressant and can effectively prevent graft rejection [23,24]. Many studies [23–27] reported that the occurrence of rejection after corneal allografting was increased significantly in the absence of FasL. On the other hand, some other studies [28,29] demonstrated that the Fas/Fas-L system regulated immunoresponse by inducing cell apoptosis, and Fas-L expression could effectively inhibit inflammatory response. "
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    ABSTRACT: It is generally accepted that high osmotic pressure (HOP) of lacrimal fluid is the core mechanism causing ocular inflammation and injury. However, the association between HOP and the regulation of cell inflammatory response and apoptotic pathways remains unclear. In the present study, we used HOP to interfere with in vitro cultured rabbit corneal epithelial cells, and found that HOP increased the generation of reactive oxygen species (ROS) in rabbit corneal epithelial cells, and increased ROS in turn induced the activation of JNK inflammatory signaling pathway, which further promoted the expression of pro-inflammatory factor NF-κβ and induced the generation of inflammatory factor IL-1β and TNF-α. In addition, HOP-induced ROS in rabbit corneal epithelial cells regulated the CD95/CD95L-mediated cell apoptotic signaling pathway by activating JNK inflammatory signaling pathway. These findings may serve as new theoretical basis and a new way of thinking about the treatment of ocular diseases, especially dry eye.
    PLoS ONE 08/2013; 8(8):e72900. DOI:10.1371/journal.pone.0072900 · 3.23 Impact Factor
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    • "Activation of caspase- 8 initiates downstream apoptotic processes that include the activation of caspases-3, -6, -7, and mitochondrial damage [32]. The role of Fas-FasL pathway in the death of lymphocytes has been studied extensively [20], while a few reports have discussed its potential participation in degenerative disorders of the brain [5] [10] [13]. Caspase-8 has been implicated to play a non-redundant role in the extrinsic apoptotic pathway in normal tissues, solid tumors, and leukemias. "
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    ABSTRACT: Methamphetamine administration can cause neuronal apoptotic death in the rat brain via activation of the extrinsic cell death pathway (Fas ligand/Fas/caspase-8 cascade). In the present study, we injected mice with a toxic regimen of methamphetamine (10mg/kg×4 given at 2-h intervals) to assess the role of the Fas ligand/Fas/caspase-8 death pathway in their brain. Methamphetamine did cause the appearance of TUNEL-positive cells in the frontal cortex, striatum, and hippocampus of these animals. The number of TUNEL-positive cells was higher in the striatum than in the frontal cortex and hippocampus. Immunohistochemical and immunoblot techniques revealed significant methamphetamine-induced increases in Fas ligand expression and diffuse appearance of the active caspase-8 in these brain regions. Taken together, our data suggest that methamphetamine can cause marked activation of the caspase-8-dependent death pathway in the brain.
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