title: Syntaxin 11 is required for NK and CD8⁺ T-cell cytotoxicity and neutrophil degranulation.
abstract: Syntaxin 11 (STX11) controls vesicular trafficking and is a key player in exocytosis. Since Stx11 mutations are causally associated with a familial hemophagocytic lymphohistio-cytosis, we wanted to clarify whether STX11 is functionally important for key immune cell populations. This was studied in primary cells obtained from newly generated Stx11(-/-)  mice. Our data revealed that STX11 is not only widely expressed in different immune cells, but also induced upon LPS or IFN-γ treatment. However, Stx11 deficiency does not affect macrophage phagocytic function and cytokine secretion, mast cell activation, or antigen presentation by DCs. Instead, STX11 selectively controls lymphocyte cytotoxicity in NK and activated CD8(+)  T cells and degranulation in neutrophils. Stx11(-/-)  NK cells and CTLs show impaired degranulation, despite a comparable activation, maturation and expression of the complex-forming partners MUNC18-2 and VTI1B. In addition, Stx11(-/-)  CTLs and NK cells produce abnormal levels of IFN-γ. Since functional reconstitution rescues the defective phenotype of Stx11(-/-)  CTLs, we suggest a direct, specific and key role of STX11 in controlling lymphocyte cytotoxicity, cytokine production and secretion. Finally, we show that these mice are a very useful tool for dissecting the role of STX11 in vesicular trafficking and secretion.
authors.affiliation: Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany.
authors.forename: Orietta
authors.initials: O
authors.lastname: D'Orlando
authors.forename: Fang
authors.initials: F
authors.lastname: Zhao
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kasper
authors.forename: Zane
authors.initials: Z
authors.lastname: Orinska
authors.forename: Jürgen
authors.initials: J
authors.lastname: Müller
authors.forename: Irm
authors.initials: I
authors.lastname: Hermans-Borgmeyer
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Griffiths
authors.forename: Udo
authors.initials: U
authors.lastname: Zur Stadt
authors.forename: Silvia
authors.initials: S
authors.lastname: Bulfone-Paus
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015550:Cell Degranulation / Q000235:genetics; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051938:Munc18 Proteins / Q000276:immunology; D009154:Mutation / Q000235:genetics; D009504:Neutrophils / Q000276:immunology*; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000276:immunology*; D050766:Qb-SNARE Proteins / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D051938:Munc18 Proteins; D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; C491415:Vti1b protein, mouse; D007371:Interferon-gamma