Expression and subcellular localization of syntaxin 11 in human neutrophils

Xie, Li; Iglesia-Vicente, Janis de la; Yun-xiang, Fang; Mollinedo, Faustino

doi:10.1007/s00011-009-0006-x

Cited by 12 publications

(9 citation statements)

References 36 publications

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“…STX11 has been reported to be up-regulated in DCs following LPS activation but Stx11 deficiency did not appear to affect DC function ( 20 ). STX11 has also been indicated to regulate other cells of the immune system such as NK, CD8 + T cells, macrophage, platelets, and in human blood neutrophils where up-regulation of STX11 mRNA expression during differentiation has been reported ( 19 – 21 ). While it is clear from our study that STX11 regulation in DCs may be important we did not find a definitive correlation for this SNARE with the profile of cytokines or chemokines being secreted by the DCs.…”

Section: Discussionmentioning

confidence: 99%

A Role for Syntaxin 3 in the Secretion of IL-6 from Dendritic Cells Following Activation of Toll-Like Receptors

et al. 2015

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The role of dendritic cells (DCs) in directing the immune response is due in part to their capacity to produce a range of cytokines. Importantly, DCs are a source of cytokines, which can promote T cell survival and T helper cell differentiation. While it has become evident that soluble-N-ethylmaleimide-sensitive-factor accessory-protein receptors (SNAREs) are involved in membrane fusion and ultimately cytokine release, little is known about which members of this family facilitate the secretion of specific cytokines from DCs. We profiled mRNA of 18 SNARE proteins in DCs in response to activation with a panel of three Toll-like receptors (TLR) ligands and show differential expression of SNAREs in response to their stimulus and subsequent secretion patterns. Of interest, STX3 mRNA was up-regulated in response to TLR4 and TLR7 activation but not TLR2 activation. This correlated with secretion of IL-6 and MIP-1α. Abolishment of STX3 from DCs by RNAi resulted in the attenuation of IL-6 levels and to some extent MIP-1α levels. Analysis of subcellular location of STX3 by confocal microscopy showed translocation of STX3 to the cell membrane only in DCs secreting IL-6 or MIP-1α, indicating a role for STX3 in trafficking of these immune mediators. Given the role of IL-6 in Th17 differentiation, these findings suggest the potential of STX3 as therapeutic target in inflammatory disease.

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Section: Discussionmentioning

confidence: 99%

A Role for Syntaxin 3 in the Secretion of IL-6 from Dendritic Cells Following Activation of Toll-Like Receptors

et al. 2015

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“…Given that 1) STX3, STX11, and VAMP1 are up-regulated during the differentiation process in HL-60 cells, 2) STX11 and VAMP1 had already been implicated in granule exocytosis in neutrophils [29][30][31][32], and 3) no study has ever considered the functional role of STX3 in neutrophils, we investigated whether STX3 is required for cytokine release in dHL-60 cells.…”

Section: Endogenous Expression Of V-and T-snares In Myeloid Cellsmentioning

confidence: 99%

An essential role of syntaxin 3 protein for granule exocytosis and secretion of IL-1α, IL-1β, IL-12b, and CCL4 from differentiated HL-60 cells

Naegelen

Plançon

Nicot

et al. 2014

Journal of Leukocyte Biology

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Besides their roles in the killing of pathogens, neutrophils have the capacity to package a variety of cytokines into cytoplasmic granules for subsequent release upon inflammatory conditions. Because the rapid secretion of cytokines orchestrates the action of other immune cells at the infection site and thus, can contribute to the development and chronicity of inflammatory diseases, we aimed to determine the intracellular SNARE machinery responsible for the regulation of cytokine secretion and degranulation. From a constructed gene-expression network, we first selected relevant cytokines for functional validation by the CBA approach. We established a cytokine-secretion profile for human neutrophils and dHL-60 cells, underlining their similar ability to secrete a broad variety of cytokines within proinflammatory conditions mimicked by LPS stimulation. Secondly, after screening of SNARE genes by microarray experiments, we selected STX3 for further functional studies. With the use of a siRNA strategy, we show that STX3 is clearly required for the maximal release of IL-1α, IL-1β, IL-12b, and CCL4 without alteration of other cytokine secretion in dHL-60 cells. In addition, we demonstrate that STX3 is involved in MMP-9 exocytosis from gelatinase granules, where STX3 is partly localized. Our results suggest that the secretion of IL-1α, IL-1β, IL-12b, and CCL4 occurs during gelatinase degranulation, a process controlled by STX3. In summary, these findings provide first evidence that STX3 has an essential role in trafficking pathways of cytokines in neutrophil granulocytes.

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“…STX11 is expressed in a wide variety of cells including human monocytes/macrophages, neutrophils, B cells, NK cells and CD8 + T cells [2][3][4][5][6][7][8][9]. STX11 is enriched in immune tissues such as thymus, spleen C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur.…”

Section: Introductionmentioning

confidence: 99%

“…de and is involved in intracellular membrane trafficking events by interacting with other family members or by associating with membranes by palmitoylation of cysteine residues [1][2][3]. STX11 is expressed in a wide variety of cells including human monocytes/macrophages, neutrophils, B cells, NK cells and CD8 + T cells [2][3][4][5][6][7][8][9]. STX11 is enriched in immune tissues such as thymus, spleen Values represent the mean ± SEM percentage of cell subsets in the spleen (n = 8) and lymph nodes (WT n = 7; Stx11 −/− n = 6) and are the summary of three experiments performed.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, even though STX11 expression is regulated upon cell activation, it is dispensable for BMMC degranulation. Since STX11 has been described to be highly expressed in human neutrophils [7], the role of STX11 deficiency in the murine counterparts was investigated. To this purpose, the degranulation activity of Stx11 −/− neutrophils was compared with that of WT cells by measuring LAMP-1/CD107a translocation and release of neutrophil-specific β-glucuronidase upon stimulation with PMA/ionomycin or fMLP.…”

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

et al. 2012

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Syntaxin 11 (STX11) controls vesicular trafficking and is a key player in exocytosis. SinceStx11 mutations are causally associated with a familial hemophagocytic lymphohistiocytosis, 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. Keywords: CTL r Cytokines r Exocytosis r N-ethylmaleimide-sensitive factor attachment protein receptorSee accompanying Commentary by Lopez and Voskoboinik.Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionSyntaxin 11 (STX11) belongs to the family of N-ethylmaleimidesensitive factor attachment protein receptor (SNARE) proteins Correspondence: Prof. Silvia Bulfone-Paus e-mail: sbulfone@fz-borstel.de and is involved in intracellular membrane trafficking events by interacting with other family members or by associating with membranes by palmitoylation of cysteine residues [1][2][3]. STX11 is expressed in a wide variety of cells including human monocytes/macrophages, neutrophils, B cells, NK cells and CD8 + T cells [2][3][4][5][6][7][8][9]. STX11 is enriched in immune tissues such as thymus, spleen C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2013. 43: 194-208 Immunomodulation 195 Values represent the mean ± SEM percentage of cell subsets in the spleen (n = 8) and lymph nodes (WT n = 7; Stx11 −/− n = 6) and are the summary of three experiments performed.and lymph nodes, but lower levels of protein are detectable also in heart, kidney and liver [2]. STX11 localizes mainly in the vesicular tubular clusters, an organelle complex between the endoplasmic reticulum and the Golgi, and displays, in addition, a spotted staining pattern throughout the cell periphery [2,9]. While STX11 has been recognized to act as a negative regulator of both phagocytosis and intracellular trafficking between endosomes, lysosomes and the outer membrane in macrophages [6,9], in human NK cells and CTLs, ST...

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Expression and subcellular localization of syntaxin 11 in human neutrophils

Abstract: These data indicate that human neutrophils express syntaxin 11 and call attention to the possible involvement of neutrophils in familial hemophagocytic lymphohistiocytosis pathology.

Cited by 12 publications

References 36 publications

A Role for Syntaxin 3 in the Secretion of IL-6 from Dendritic Cells Following Activation of Toll-Like Receptors

A Role for Syntaxin 3 in the Secretion of IL-6 from Dendritic Cells Following Activation of Toll-Like Receptors

An essential role of syntaxin 3 protein for granule exocytosis and secretion of IL-1α, IL-1β, IL-12b, and CCL4 from differentiated HL-60 cells

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

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Expression and subcellular localization of syntaxin 11 in human neutrophils

Abstract: These data indicate that human neutrophils express syntaxin 11 and call attention to the possible involvement of neutrophils in familial hemophagocytic lymphohistiocytosis pathology.

Cited by 12 publications

References 36 publications

A Role for Syntaxin 3 in the Secretion of IL-6 from Dendritic Cells Following Activation of Toll-Like Receptors

A Role for Syntaxin 3 in the Secretion of IL-6 from Dendritic Cells Following Activation of Toll-Like Receptors

An essential role of syntaxin 3 protein for granule exocytosis and secretion of IL-1α, IL-1β, IL-12b, and CCL4 from differentiated HL-60 cells

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

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