title: Primary hemophagocytic syndromes point to a direct link between lymphocyte cytotoxicity and homeostasis.
abstract: Hemophagocytic syndrome (HS) is a severe and often fatal syndrome resulting from potent and uncontrolled activation and proliferation of T-lymphocytes, leading to excessive macrophage activation and multiple deleterious effects. The onset of HS characterizes several inherited disorders in humans. In each condition, the molecular defect impairs the granule-dependent cytotoxic activity of lymphocytes, thus highlighting the determinant role of this function in driving the immune system to a state of equilibrium following infection. It has also been shown that some of the proteins required for lytic granule secretion are required for melanocyte function, leading to associated hypopigmentation in these conditions. This review focuses on several effectors of this secretory pathway, recently identified, because their defects cause these disorders, and discusses their role and molecular interactions in granule-dependent cytotoxic activity.
authors.affiliation: INSERM U429, Hôpital Necker Enfants-Malades, Paris, France.
authors.forename: Gael
authors.initials: G
authors.lastname: Ménasché
authors.forename: Jérôme
authors.initials: J
authors.lastname: Feldmann
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Geneviève
authors.initials: G
authors.lastname: de Saint Basile
mesh_terms: D003602:Cytotoxicity, Immunologic; D015616:Histiocytosis, Non-Langerhans-Cell / Q000235:genetics* / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D020460:Melanosomes / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013577:Syndrome; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000502:physiology; D000075745:rab27 GTP-Binding Proteins
chemical_list: D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D052899:Pore Forming Cytotoxic Proteins; C485548:UNC13B protein, human; D000075745:rab27 GTP-Binding Proteins; D054353:Perforin; C066694:RAB27A protein, human; D020691:rab GTP-Binding Proteins