Functional characterisation of Munc18–2 missense mutations in patients with familial hemophagocytic lymphohistiocytosis type 5 (FHL-5)

Upon activation, cytotoxic T-Lymphocytes (CTLs) and Natural Killer cells use a rapid intracellular transport system for the regulated exocytosis of lytic granules through the immunological synapse in order to eliminate infected target cells. In patients with familial hemophagocytic lymphohistiocytosis (FHL), a genetically heterogeneous autosomal-recessive disorder characterised by a severe hyperinflammatory phenotype, this highly regulated process is disturbed. We recently identified STXBP2 encoding Syntaxin binding protein 2 (Munc18–2), which is involved in the regulation of vesicle transport, as a novel FHL-as…