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Inherited defects causing hemophagocytic lymphohistiocytic syndrome
Author(s) -
de Saint Basile Geneviève,
Ménasché Gaël,
Latour Sylvain
Publication year - 2011
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2011.06307.x
Subject(s) - perforin , cytotoxic t cell , granulysin , granzyme , microbiology and biotechnology , exocytosis , cytolysis , chemistry , priming (agriculture) , degranulation , biology , immunology , secretion , biochemistry , receptor , in vitro , botany , germination
Hemophagocytic lymphohistiocytosis (HLH) manifests as the uncontrolled activation of T lymphocytes and macrophages infiltrating multiple organs. Molecular studies of individuals with HLH have demonstrated in most of these conditions a critical role of granule‐dependent cytotoxic activity in the regulation of lymphocyte homeostasis, and have allowed the characterization of key effectors regulating cytotoxic granule release. The cytolytic process may now be considered a multistep process, including cell activation; the polarization of cytotoxic granules toward the conjugated target cell; the tethering, priming, and fusion of the cytotoxic granules with the plasma membrane; and the release of their contents (perforin and granzymes) into the intercellular cleft, leading to target cell death. Cytolytic cells have a second effector function involving the production of cytokines, principally γ‐interferon, which is secreted independently of the exocytosis cytotoxic granule pathway. An analysis of the mechanisms underlying HLH has identified γ‐interferon as a key cytokine inducing uncontrolled macrophage activation, and thus represents a potential therapeutic target.