Fas stimulation of T lymphocytes promotes rapid intercellular exchange of death signals via membrane nanotubes

Arkwright, Peter D.; Luchetti, Francesca; Tour, Julien; Roberts, Charlotte F.; Ayub, Rahna; Morales, Ana Paula; Rodrı́guez, José J.; Gilmore, Andrew; Canonico, Barbara; Papa, Stefano; Esposti, Mauro Degli

doi:10.1038/cr.2009.112

Cited by 99 publications

(126 citation statements)

References 37 publications

Supporting

Mentioning

118

Contrasting

Unclassified

Order By: Relevance

“…Our study further identified CDC42, a known regulator of actin organization, as a novel mediator of IPT in senescent cells. In line with our results, inhibition of CDC42 was shown to block TNT formation in T cells (Arkwright et al 2010), suggesting that the reduction in protein transfer following CDC42 knockdown or inhibition may be due to lack of CB formation. Identifying CDC42 activity as a key regulator of CB formation in senescent cells provides molecular insight that could be exploited to prevent IPT in pathological conditions.…”

Section: Discussionsupporting

confidence: 91%

Senescent cells communicate via intercellular protein transfer

et al. 2015

View full text Add to dashboard Cite

Mammalian cells mostly rely on extracellular molecules to transfer signals to other cells. However, in stress conditions, more robust mechanisms might be necessary to facilitate cell-cell communications. Cellular senescence, a stress response associated with permanent exit from the cell cycle and the development of an immunogenic phenotype, limits both tumorigenesis and tissue damage. Paradoxically, the long-term presence of senescent cells can promote tissue damage and aging within their microenvironment. Soluble factors secreted from senescent cells mediate some of these cell-nonautonomous effects. However, it is unknown whether senescent cells impact neighboring cells by other mechanisms. Here we show that senescent cells directly transfer proteins to neighboring cells and that this process facilitates immune surveillance of senescent cells by natural killer (NK) cells. We found that transfer of proteins to NK and T cells is increased in the murine preneoplastic pancreas, a site where senescent cells are present in vivo. Proteomic analysis and functional studies of the transferred proteins revealed that the transfer is strictly dependent on cell-cell contact and CDC42-regulated actin polymerization and is mediated at least partially by cytoplasmic bridges. These findings reveal a novel mode of intercellular communication by which senescent cells regulate their immune surveillance and might impact tumorigenesis and tissue aging.

show abstract

Section: Discussionsupporting

confidence: 91%

Senescent cells communicate via intercellular protein transfer

et al. 2015

View full text Add to dashboard Cite

show abstract

“…CD41 T cells and Jurkat cells were both treated with FasL at a final concentration of 0.5 lg/ml for a maximum of 2 h. Our previous findings (7) showed that Fas stimulation led to an intriguing (and previously unsuspected) asymmetry of death propagation according to cell conjugation and rapidly induced extensive membrane nanotube formation between neighboring T cells. The experiments were performed using flow cytometric (FC) and morphologic (fluorescence and time lapse) analyses.…”

Section: Fasl Stimulation Of T Cellsmentioning

confidence: 95%

Flow cytometric analyses disclose intercellular communications in FasL‐stimulated T cells: Results and trouble shooting

et al. 2011

View full text Add to dashboard Cite

LIFE depends on the ability of cells to communicate with one another. Much of this crosstalk occurs at cell-cell contacts and is regulated by complex structural interface: neurological and immunological synapses that transmit cell-cell signals through the extracellular space, relying on mechanisms of ligand-receptor signalling across tight cell-cell junctions. In addition to these well-known examples, other cellular structures involved in cell-cell communication have been identified (1). A frequent result of cell-cell communication is collective population behavior that can potentially lead to complex phenotypes not observed in separate individual cells, for example, in development or tumor formation (2,3). Immune responses against pathogens or any foreign antigens require fine immune regulation, where cellular communications are mediated by either soluble or cell surface molecules. Generally, absorption, exosome production and uptake, internalization, and membrane nanotube formation are the probable mechanisms through which the membrane fragments and cytoplasmic content are transferred from one cell to another (4). The identification of new structures involved in cell-to-cell communication has led to the development of new analytical and imaging tools, which have allowed us to enhance our understanding of the ubiquitous phenomenon of cell-to-cell communication. Such tools include quantitative cell microscopy, now mainly represented by two distinct techniques: flow cytometry (FCM) and image cytometry (IC) (5). FCM allows analysis of cell suspensions, cell-by-cell quantification of optical signals, rapid analysis (several hundred cells per second), and cell sorting, whereas IC allows precise localization and quantification of optical signals emitted by each point of the observed field and image analysis (morphology and morphometry). FASL STIMULATION OF T CELLSThe Fas/CD95 surface receptor mediates rapid death of various cell types, including autoreactive T cells, which can trigger autoimmunity. In this study we investigate novel aspects of Fas signaling that define a ''social'' dimension to receptor-induced apoptosis. At least in some cell types, FasL can be stored in granules and then rapidly released at the cell surface in response to external stimuli. Alternatively, FasL can be cleaved from the membrane by matrix metalloproteases and act as a soluble cytokine (6). In its membrane-bound form, FasL acts as a ligand for Fas and can trigger Fas-induced death.In our experiments, CD41 T cells were purified from PBMC by negative selection using the MACS system. CD41 T cells and Jurkat cells were both treated with FasL at a final concentration of 0.5 lg/ml for a maximum of 2 h. Our previous findings (7) showed that Fas stimulation led to an intriguing (and previously unsuspected) asymmetry of death propagation according to cell conjugation and rapidly induced extensive membrane nanotube formation between neighboring T cells. The experiments were performed using flow cytometric (FC) and morphologic (fluorescence and ti...

show abstract

“…In ovarian follicles, numerous extensions from cumulus cells traverse the zona pellucida and come to interact with the oocyte surface by a gap junction before ovulation [37]. [40] …”

Section: M-sec a Clue For Understanding The Molecular Mechanisms Of mentioning

confidence: 99%

Tunneling nanotubes: Emerging view of their molecular components and formation mechanisms

Kimura

Hase

Ohno

2012

Experimental Cell Research

View full text Add to dashboard Cite

Fas stimulation of T lymphocytes promotes rapid intercellular exchange of death signals via membrane nanotubes

Cited by 99 publications

References 37 publications

Senescent cells communicate via intercellular protein transfer

Senescent cells communicate via intercellular protein transfer

Flow cytometric analyses disclose intercellular communications in FasL‐stimulated T cells: Results and trouble shooting

Tunneling nanotubes: Emerging view of their molecular components and formation mechanisms

Contact Info

Product

Resources

About