Primary hemophagocytic syndromes point to a direct link between lymphocyte cytotoxicity and homeostasis.
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.
Ménasché
Gael
G
INSERM U429, Hôpital Necker Enfants-Malades, Paris, France.
Feldmann
Jérôme
J
Fischer
Alain
A
de Saint Basile
Geneviève
G
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
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