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P2X7 purinergic receptor plays a critical role in maintaining T-cell homeostasis and preventing lupus pathogenesis.
Front Immunol
October 2022
UMR 996, INSERM, Université Paris-Saclay, Clamart, France.
The severe lymphoproliferative and lupus diseases developed by MRL/ mice depend on interactions between the Fas mutation and MRL genetic background. Thus, the Fas mutation causes limited disease in C57BL/6 mice. We previously found that accumulating B220 CD4CD8 double negative (DN) T cells in MRL/ mice show defective P2X7 receptor ( P2X7)-induced cellular functions, suggesting that P2X7 contributes to T-cell homeostasis, along with Fas.
View Article and Find Full Text PDFEarly B cell factor 4 modulates FAS-mediated apoptosis and promotes cytotoxic function in human immune cells.
Proc Natl Acad Sci U S A
August 2022
Molecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Apoptosis is a genetically regulated program of cell death that plays a key role in immune disease processes. We identified EBF4, a little-studied member of the early B cell factor (EBF) family of transcription factors, in a whole-genome CRISPR screen for regulators of Fas/APO-1/CD95-mediated T cell death. Loss of EBF4 increases the half-life of the c-FLIP protein, and its presence in the Fas signaling complex impairs caspase-8 cleavage and apoptosis.
View Article and Find Full Text PDFSRSF6 Regulates the Alternative Splicing of the Apoptotic Fas Gene by Targeting a Novel RNA Sequence.
Cancers (Basel)
April 2022
School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Korea.
Alternative splicing (AS) is a procedure during gene expression that allows the production of multiple mRNAs from a single gene, leading to a larger number of proteins with various functions. The alternative splicing (AS) of Fas (Apo-1/CD95) pre-mRNA can generate membrane-bound or soluble isoforms with pro-apoptotic and anti-apoptotic functions. SRSF6, a member of the Serine/Arginine-rich protein family, plays essential roles in both constitutive and alternative splicing.
View Article and Find Full Text PDFDisruption of the FasL/Fas axis protects against inflammation-derived tumorigenesis in chronic liver disease.
Cell Death Dis
February 2019
Department of Internal Medicine III, University Hospital, RWTH Aachen, Aachen, Germany.
Article Synopsis
- Fas Ligand (FasL) and Fas are involved in apoptosis and their role was studied in a model of chronic liver disease using NEMO knockout mice.
- The study found that Fas mutation in NEMO mice led to less liver damage, increased survival of liver cells, and lower liver fibrosis markers compared to standard NEMO mice.
- At 52 weeks, NEMO/Fas mice showed reduced liver cancer growth, fewer tumors, and decreased inflammation, suggesting that targeting the Fas signaling pathway could be a promising approach for treating chronic liver disease and associated cancers.
Modulation of SIV and HIV DNA vaccine immunity by Fas-FasL signaling.
Viruses
March 2015
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Article Synopsis
- The study investigates the role of the Fas/Apo-1/CD95 death receptor in enhancing virus-specific cell-mediated immune (CMI) responses during DNA vaccination and LCMV infections in mice.
- Researchers tested various pro- and anti-apoptotic molecules and found that while Fas or FasL knockout mice had improved immune responses, manipulating these signals through shRNA or antibodies did not yield the same results, leading to increased regulatory T cells (Treg).
- Two adjuvant molecules, FADD and cFLIP, were identified that significantly improved immune responses and T cell proliferation, enabling some mice to clear a persistent variant of LCMV that typically evades the immune system.
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