Related resources
Full-text held externally
- PMID: 23042080
- UKPMCID: 23042080
- DOI: 10.1002/eji.201142343
Search for item elsewhere
University researcher(s)
Academic department(s)
Syntaxin 11 is required for NK and CD8⁺ T-cell cytotoxicity and neutrophil degranulation.
D'Orlando, Orietta; Zhao, Fang; Kasper, Brigitte; Orinska, Zane; Müller, Jürgen; Hermans-Borgmeyer, Irm; Griffiths, Gillian M; Zur Stadt, Udo; Bulfone-Paus, Silvia
European journal of immunology. 2013;43(1):194-208.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:
Full-text held externally
- PMID: 23042080
- UKPMCID: 23042080
- DOI: 10.1002/eji.201142343
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.