Syntaxin 11 is required for NK and CD8⁺ T-cell cytotoxicity and neutrophil degranulation

Eur J Immunol. 2013 Jan;43(1):194-208. doi: 10.1002/eji.201142343. Epub 2012 Dec 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Degranulation / genetics
  • Cell Line
  • Cytotoxicity, Immunologic / genetics
  • Humans
  • Interferon-gamma / immunology
  • Killer Cells, Natural / immunology*
  • Lipopolysaccharides / immunology
  • Lymphohistiocytosis, Hemophagocytic / genetics
  • Lymphohistiocytosis, Hemophagocytic / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Munc18 Proteins / immunology
  • Mutation / genetics
  • Neutrophils / immunology*
  • Qa-SNARE Proteins / genetics
  • Qa-SNARE Proteins / immunology*
  • Qb-SNARE Proteins / immunology


  • Lipopolysaccharides
  • Munc18 Proteins
  • Qa-SNARE Proteins
  • Qb-SNARE Proteins
  • Vti1b protein, mouse
  • Interferon-gamma