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

Autor: Gillian M. Griffiths, Udo zur Stadt, Fang Zhao, Brigitte Kasper, Jürgen Müller, Silvia Bulfone-Paus, Irm Hermans-Borgmeyer, Zane Orinska, Orietta D'Orlando
Rok vydání: 2012
Předmět:
Zdroj: European Journal of Immunology. 43:194-208
ISSN: 0014-2980
DOI: 10.1002/eji.201142343
Popis: 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-? 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-?. 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.
Databáze: OpenAIRE
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