Critical role of extracellular vesicles in modulating the cellular effects of cytokines

Szabó, Gitta; Tarr, Bettina; Pálóczi, Krisztina; Éder, Katalin; Lajkó, Eszter; Kittel, Ágnes; Tóth, Sára; György, Bence; Pásztói, Mária; Németh, Andrea H.; Osteikoetxea, Xabier; Pállinger, Éva; Falus, András; Szabó-Taylor, Katalin; Buzás, Edit I.

doi:10.1007/s00018-014-1618-z

Cited by 44 publications

(42 citation statements)

References 40 publications

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“…MVs were isolated from mLN‐ and pLN‐iFRCs as described above, followed by TRPS analysis using qNano instrument (IZON Sciences Ltd.) as described previously . Carboxylated polystyrene particle standards were used to determine the vesicle size.…”

Section: Methodsmentioning

confidence: 99%

Mesenteric lymph node stromal cell‐derived extracellular vesicles contribute to peripheral de novo induction of Foxp3⁺ regulatory T cells

et al. 2017

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Intestinal regulatory T cells (Tregs) are fundamental in peripheral tolerance toward commensals and food‐borne antigens. Accordingly, gut‐draining mesenteric lymph nodes (mLNs) represent a site of efficient peripheral de novo Treg induction when compared to skin‐draining peripheral LNs (pLNs), and we had recently shown that LN stromal cells substantially contribute to this process. Here, we aimed to unravel the underlying molecular mechanisms and generated immortalized fibroblastic reticular cell lines (iFRCs) from mLNs and pLNs, allowing unlimited investigation of this rare stromal cell subset. In line with our previous findings, mLN‐iFRCs showed a higher Treg‐inducing capacity when compared to pLN‐iFRCs. RNA‐seq analysis focusing on secreted molecules revealed a more tolerogenic phenotype of mLN‐ as compared to pLN‐iFRCs. Remarkably, mLN‐iFRCs produced substantial numbers of microvesicles (MVs) that carried elevated levels of TGF‐β when compared to pLN‐iFRC‐derived MVs, and these novel players of intercellular communication were shown to be responsible for the tolerogenic properties of mLN‐iFRCs. Thus, stromal cells originating from mLNs contribute to peripheral tolerance by fostering de novo Treg induction using TGF‐β‐carrying MVs. This finding provides novel insights into the subcellular/molecular mechanisms of de novo Treg induction and might serve as promising tool for future therapeutic applications to treat inflammatory disorders.

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Section: Methodsmentioning

confidence: 99%

Mesenteric lymph node stromal cell‐derived extracellular vesicles contribute to peripheral de novo induction of Foxp3⁺ regulatory T cells

et al. 2017

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“…5,13 At least 500 particles were counted (except when lysis was observed in which case one minute recording time was used regardless of particle counts). NP100, NP400, NP800 and NP2000 nanopore membranes stretched between 43-47 mm were used.…”

Section: Detergent Treatment Of Extracellular Vesiclesmentioning

confidence: 99%

Differential detergent sensitivity of extracellular vesicle subpopulations

et al. 2015

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a Extracellular vesicles (including exosomes, microvesicles and apoptotic bodies) are currently attracting rapidly increasing attention from various fields of biology due to their ability to carry complex information and act as autocrine, paracrine and even endocrine intercellular messengers. In the present study we investigated the sensitivity of size-based subpopulations of extracellular vesicles to different concentrations of detergents including sodium dodecyl sulphate, Triton X-100, Tween 20 and deoxycholate. We determined the required detergent concentration that lysed each of the vesicle subpopulations secreted by Jurkat, THP-1, MiaPaCa and U937 human cell lines. We characterized the vesicles by tunable resistive pulse sensing, flow cytometry and transmission electron microscopy. Microvesicles and apoptotic bodies were found to be more sensitive to detergent lysis than exosomes. Furthermore, we found evidence that sodium dodecyl sulphate and Triton X-100 were more effective in vesicle lysis at low concentrations than deoxycholate or Tween 20. Taken together, our data suggest that a combination of differential detergent lysis with tunable resistive pulse sensing or flow cytometry may prove useful for simple and fast differentiation between exosomes and other extracellular vesicle subpopulations as well as between vesicular and non-vesicular structures.

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“…[61] For example,m icrovesicles are important carriers of cytokines and chemokines.T hese proteins can induce cell and tissue response,w hich can have am ultitude of therapeutic or pathological effects. [46,60]…”

Section: Microvesiclesmentioning

confidence: 99%

Vesicles in Nature and the Laboratory: Elucidation of Their Biological Properties and Synthesis of Increasingly Complex Synthetic Vesicles

et al. 2017

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The important role of vesicles in many aspects of cell function is well-recognized, but only recently have sophisticated imaging techniques begun to reveal their ubiquity in nature. While we further our understanding of the biological properties of vesicles and their physiological functions, increasingly elegant artificial vesicles are being developed for a wide range of technological applications and basic research. Herein, we examine the state of the art of biological and synthetic vesicles and place their biological features in the context of recent synthetic developments, thus providing a unique overview of these complex and rapidly developing fields. The challenges and opportunities associated with future biological and synthetic studies of vesicles are also presented.

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Critical role of extracellular vesicles in modulating the cellular effects of cytokines

Cited by 44 publications

References 40 publications

Mesenteric lymph node stromal cell‐derived extracellular vesicles contribute to peripheral de novo induction of Foxp3⁺ regulatory T cells

Mesenteric lymph node stromal cell‐derived extracellular vesicles contribute to peripheral de novo induction of Foxp3⁺ regulatory T cells

Differential detergent sensitivity of extracellular vesicle subpopulations

Vesicles in Nature and the Laboratory: Elucidation of Their Biological Properties and Synthesis of Increasingly Complex Synthetic Vesicles

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Critical role of extracellular vesicles in modulating the cellular effects of cytokines

Cited by 44 publications

References 40 publications

Mesenteric lymph node stromal cell‐derived extracellular vesicles contribute to peripheral de novo induction of Foxp3+ regulatory T cells

Mesenteric lymph node stromal cell‐derived extracellular vesicles contribute to peripheral de novo induction of Foxp3+ regulatory T cells

Differential detergent sensitivity of extracellular vesicle subpopulations

Vesicles in Nature and the Laboratory: Elucidation of Their Biological Properties and Synthesis of Increasingly Complex Synthetic Vesicles

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Mesenteric lymph node stromal cell‐derived extracellular vesicles contribute to peripheral de novo induction of Foxp3⁺ regulatory T cells

Mesenteric lymph node stromal cell‐derived extracellular vesicles contribute to peripheral de novo induction of Foxp3⁺ regulatory T cells