title: Cell-death signaling and human disease.
abstract: The autoimmune lymphoproliferative syndrome (ALPS) in humans and the lpr mouse strain are the first examples of primary apoptosis defects caused by inherited death-receptor mutations. They illustrate the role of Fas and Fas ligand in the control of autoimmune T-cell and B-cell proliferation. Subsequent analyses of ALPS in humans have highlighted the role of caspase 10 in the induction of apoptosis. The recent identification of a human caspase 8 defect has revealed a potential connection between apoptosis pathways and immune-receptor signaling. The genetic basis of ALPS is extremely complex, as multiple factors are potentially involved in the pathogenesis of this disease, thus offering an interesting model with which to unravel the mechanisms involved in T-cell homeostasis and self-tolerance.
authors.affiliation: Institut National de la santé et de la Recherche Médicale U429, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France. rieux@necker.fr
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rieux-Laucat
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Françoise Le
authors.initials: FL
authors.lastname: Deist
mesh_terms: D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D053222:Fas Ligand Protein; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D018448:Models, Immunological; D015398:Signal Transduction; D013577:Syndrome
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins