Syntaxin 11 is required for NK and CD8⁺ T-cell cytotoxicity and neutrophil degranulation.
Standard
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.
in: EUR J IMMUNOL, Jahrgang 43, Nr. 1, 1, 2013, S. 194-208.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Syntaxin 11 is required for NK and CD8⁺ T-cell cytotoxicity and neutrophil degranulation.
AU - D'Orlando, Orietta
AU - Zhao, Fang
AU - Kasper, Brigitte
AU - Orinska, Zane
AU - Müller, Jürgen
AU - Hermans-Borgmeyer, Irm
AU - Griffiths, Gillian M
AU - Zur Stadt, Udo
AU - Bulfone-Paus, Silvia
N1 - © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Animals
KW - Humans
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Cell Line
KW - Mutation/genetics
KW - Interferon-gamma/immunology
KW - Neutrophils/immunology
KW - Killer Cells, Natural/immunology
KW - Cytotoxicity, Immunologic/genetics
KW - CD8-Positive T-Lymphocytes/immunology
KW - Cell Degranulation/genetics
KW - Lipopolysaccharides/immunology
KW - Lymphohistiocytosis, Hemophagocytic/genetics/immunology
KW - Munc18 Proteins/immunology
KW - Qa-SNARE Proteins/genetics/immunology
KW - Qb-SNARE Proteins/immunology
KW - Animals
KW - Humans
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Cell Line
KW - Mutation/genetics
KW - Interferon-gamma/immunology
KW - Neutrophils/immunology
KW - Killer Cells, Natural/immunology
KW - Cytotoxicity, Immunologic/genetics
KW - CD8-Positive T-Lymphocytes/immunology
KW - Cell Degranulation/genetics
KW - Lipopolysaccharides/immunology
KW - Lymphohistiocytosis, Hemophagocytic/genetics/immunology
KW - Munc18 Proteins/immunology
KW - Qa-SNARE Proteins/genetics/immunology
KW - Qb-SNARE Proteins/immunology
U2 - 10.1002/eji.201142343
DO - 10.1002/eji.201142343
M3 - SCORING: Journal article
C2 - 23042080
VL - 43
SP - 194
EP - 208
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 1
M1 - 1
ER -