Cutting Edge: Syntaxin 11 Regulates Lymphocyte-Mediated Secretion and Cytotoxicity

Little is known about the regulatory roles of specific soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in cytotoxic lymphocytes. Recent information suggests that mutations in the SNARE protein syntaxin 11 result in a form of familial hemophagocytic lymphohistio...

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Bibliographic Details
Published in:Journal of Immunology 2007-09, Vol.179 (6), p.3397-3401
Main Authors: Arneson, Laura N, Brickshawana, Adipong, Segovis, Colin M, Schoon, Renee A, Dick, Christopher J, Leibson, Paul J
Format: Article
Language:English
Subjects:
Cell Line
Cell Membrane - metabolism
Clone Cells
Cytoplasm - metabolism
Cytoplasmic Granules - metabolism
Cytotoxicity Tests, Immunologic
Exocytosis - immunology
Humans
Jurkat Cells
K562 Cells
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Qa-SNARE Proteins - biosynthesis
Qa-SNARE Proteins - physiology
T-Lymphocytes, Cytotoxic - cytology
T-Lymphocytes, Cytotoxic - immunology
T-Lymphocytes, Cytotoxic - metabolism
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Summary:Little is known about the regulatory roles of specific soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in cytotoxic lymphocytes. Recent information suggests that mutations in the SNARE protein syntaxin 11 result in a form of familial hemophagocytic lymphohistiocytosis (FHL). Because genetic abnormalities in key granule components (e.g., perforin) or in regulators of secretion (e.g., Munc13-4) underlie the other identified forms of FHL, we assessed whether syntaxin 11 might also serve a related regulatory role. We determined that syntaxin 11 is expressed in NK cells and activated CTLs and is located in discrete membrane-associated structures in the cytoplasm. Enhanced expression of syntaxin 11 augments the secretion and killing of tumor targets, and suppression of syntaxin 11 expression inhibits these functions. Our data identify and characterize a role for syntaxin 11 in granule exocytosis and in the generation of cell-mediated killing. These results also provide new insights on the mechanisms of hemopoietic dysregulation in FHL.
ISSN:0022-1767
1550-6606
1365-2567
DOI:10.4049/jimmunol.179.6.3397