Document Detail


Syntaxin 11 is required for NK and CD8⁺ T-cell cytotoxicity and neutrophil degranulation.
MedLine Citation:
PMID:  23042080     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Orietta D'Orlando; Fang Zhao; Brigitte Kasper; Zane Orinska; Jürgen Müller; Irm Hermans-Borgmeyer; Gillian M Griffiths; Udo Zur Stadt; Silvia Bulfone-Paus
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-12
Journal Detail:
Title:  European journal of immunology     Volume:  43     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-16     Completed Date:  2013-04-08     Revised Date:  2014-03-14    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  194-208     Citation Subset:  IM    
Copyright Information:
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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MeSH Terms
Descriptor/Qualifier:
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,  immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Munc18 Proteins / immunology
Mutation / genetics
Neutrophils / immunology*
Qa-SNARE Proteins / genetics,  immunology*
Qb-SNARE Proteins / immunology
Grant Support
ID/Acronym/Agency:
075880//Wellcome Trust; 100140//Wellcome Trust
Chemical
Reg. No./Substance:
0/Lipopolysaccharides; 0/Munc18 Proteins; 0/Qa-SNARE Proteins; 0/Qb-SNARE Proteins; 0/Vti1b protein, mouse; 82115-62-6/Interferon-gamma
Comments/Corrections
Comment In:
Eur J Immunol. 2013 Jan;43(1):46-9   [PMID:  23322694 ]

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