Syntaxin 11 is required for NK and CD8+ T‐cell cytotoxicity and neutrophil degranulation. Issue 1 (12th December 2012)

• Record Type: Journal Article
• Authors: D'Orlando, Orietta; Zhao, Fang; Kasper, Brigitte; Orinska, Zane; Müller, Jürgen; Hermans‐Borgmeyer, Irm; Griffiths, Gillian M.; Zur Stadt, Udo; Bulfone‐Paus, Silvia
• Is Part Of: European journal of immunology. Volume 43:Issue 1(2013:Jan.)
• Page Start: 194
• Page End: 208
• Publication Date: 2012-12-12
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201142343
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Syntaxin 11 (STX11) controls vesicular trafficking and is a key player in exocytosis. Since <italic>Stx11</italic> 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 <italic>Stx11<sup>−/−</sup></italic> 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, <italic>Stx11</italic> 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<sup>+</sup> T cells and degranulation in neutrophils. <italic>Stx11<sup>−/−</sup></italic> NK cells and CTLs show impaired degranulation<italic>, </italic> despite a comparable activation, maturation and expression of the complex‐forming partners MUNC18–2 and VTI1B. In addition, <italic>Stx11<sup>−/−</sup></italic> CTLs and NK cells produce abnormal levels of IFN‐γ. Since functional reconstitution rescues the defective phenotype of <italic>Stx11<sup>−/−</sup></italic> 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.</p> </abstract>