Subcompartments of the macrophage recycling endosome direct the differential secretion of IL-6 and TNFα

Manderson, Anthony P.; Kay, Jason G.; Hammond, Luke A.; Brown, Darren L.; Stow, Jennifer L.

doi:10.1084/jem2047oia19

Cited by 51 publications

(125 citation statements)

References 53 publications

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“…The RE network is highly compartmentalized with subcompartments that collect and sort exocytic, recycling, and endocytic cargos (Manderson et al, 2007;Marchese, 2014). Membranes that pinch off the RE network are also carriers that can fuse with the plasma membrane to deliver exocytic or secretory cargo.…”

Section: Background and Objectivementioning

confidence: 99%

“…Different cytokines traverse the REs during movement from the trans-Golgi network towards the cell surface for secretion (Manderson et al, 2007;Stow et al, 2013;Beaumont et al, 2011). Receptors can be internalized into REs and then targeted for degradation or recycling (Marchese, 2014).…”

Section: Background and Objectivementioning

confidence: 99%

“…In macrophages, the REs form a vast, interconnected network of vesicular and tubular elements that are collectively distributed from the perinuclear region to the subplasma membrane zone (Lacy & Stow, 2011;Manderson, Kay, Hammond, Brown, & Stow, 2007). This highly dynamic organellar system is crucial for the immune surveillance roles of macrophages, which include the ingestion and sampling of fluid, particulate matter and pathogens, the destruction of pathogens and cell debris, and the secretion of critical mediators like chemokines and cytokines (Epelman, Lavine, & Randolph, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Labeled REs can be readily imaged in fixed macrophages as a series of small puncta, contrasting with imaging in live cells where the dynamic connections and tubules that interconnect the RE network and provide connections to other parts of the cell, can be resolved (Manderson et al, 2007). The expression of fluorescently tagged proteins in primary macrophages and macrophage cell lines has revealed many of the unique structure/function aspects of REs in these cells.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dynamic imaging of the recycling endosomal network in macrophages

Wall

Condon

Yeo

et al. 2015

Methods in Cell Biology

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Section: Background and Objectivementioning

confidence: 99%

Section: Background and Objectivementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dynamic imaging of the recycling endosomal network in macrophages

Wall

Condon

Yeo

et al. 2015

Methods in Cell Biology

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“…Rab GTPases that mediate membrane traffic have been identified as regulators of TNF secretion in macrophages [7,8]. The Golgi complex is necessary for the transport of several secreted cytokines, and Rab6 is the quintessential and most abundant Golgi-associated Rab protein [9].…”

Section: Introductionmentioning

confidence: 99%

Identification of Rab6a as a New Target of microRNA-155 Involved in Regulating Lipopolysaccharide-Induced TNF Secretion

Yang

2015

Inflammation

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This study aims to provide experimental proof that Rab6a is an efficient target of microRNA-155 in regulating pro-inflammatory tumor necrosis factor (TNF) secretion stimulated by lipopolysaccharide (LPS) in macrophages. We identified Rab6a as a new target of microRNA-155 (miR-155) and found that overexpression of miR-155 decreased Rab6a expression at both protein and mRNA levels, which resulted in a significant reduction of TNF secretion induced by lipopolysaccharide stimulation. We have demonstrated that miR-155 can negatively regulate inflammatory TNF secretion in lipopolysaccharide stimulated macrophages, partly by targeting Rab6a, thereby providing new insights into the role of miR-155 in cytokine secretion in inflammatory macrophages.

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Secretory vesicles of immune cells contain only a limited number of interleukin 6 molecules

et al. 2018

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Immune cells communicate by releasing large quantities of cytokines. Although the mechanisms of cytokine secretion are increasingly understood, quantitative knowledge of the number of cytokines per vesicle is still lacking. Here, we measured with quantitative microscopy the release rate of vesicles potentially carrying interleukin‐6 (IL‐6) in human dendritic cells. By comparing this to the total secreted IL‐6, we estimate that secretory vesicles contain about 0.5–3 IL‐6 molecules, but with a large spread among cells/donors. Moreover, IL‐6 did not accumulate within most cells, indicating that synthesis and not trafficking is the bottleneck for IL‐6 production. IL‐6 accumulated in the Golgi apparatus only in ~ 10% of the cells. Understanding how immune cells produce cytokines is important for designing new immunomodulatory drugs.

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Subcompartments of the macrophage recycling endosome direct the differential secretion of IL-6 and TNFα

Cited by 51 publications

References 53 publications

Dynamic imaging of the recycling endosomal network in macrophages

Dynamic imaging of the recycling endosomal network in macrophages

Identification of Rab6a as a New Target of microRNA-155 Involved in Regulating Lipopolysaccharide-Induced TNF Secretion

Secretory vesicles of immune cells contain only a limited number of interleukin 6 molecules

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