Apoptotic contraction drives target cell release by cytotoxic T cells Journal Article
| Authors: | Sanchez, E. E.; Tello-Lafoz, M.; Guo, A. X. J.; de Jesus, M.; Elbanna, Y. A.; Winer, B. Y.; Budhu, S.; Chan, E. R.; Rosiek, E.; Kondo, T.; DuSold, J.; Taylor, N.; Altan-Bonnet, G.; Olson, M. F.; Huse, M. |
| Article Title: | Apoptotic contraction drives target cell release by cytotoxic T cells |
| Abstract: | Cytotoxic T lymphocytes (CTLs) fight intracellular pathogens and cancer by identifying and destroying infected or transformed target cells(1). To kill, CTLs form a specialized cytotoxic immune synapse (IS) with a target of interest and then release toxic perforin and granzymes into the interface to elicit programmed cell death(2-5). The IS then dissolves, enabling CTLs to search for additional prey and professional phagocytes to clear the corpse(6). While the mechanisms governing IS assembly have been studied extensively, far less is known about target cell release. Here, we applied time-lapse imaging to explore the basis for IS dissolution and found that it occurred concomitantly with the cytoskeletal contraction of apoptotic targets. Genetic and pharmacological perturbation of this contraction response indicated that it was both necessary and sufficient for CTL dissociation. We also found that mechanical amplification of apoptotic contractility promoted faster CTL detachment and serial killing. Collectively, these results establish a biophysical basis for IS dissolution and highlight the importance of mechanosensory feedback in the regulation of cell-cell interactions. |
| Keywords: | activation; inhibition; switch |
| Journal Title: | Nature Immunology |
| ISSN: | 1529-2908 |
| Publisher: | Nature Publishing Group |
| Publication status: | Online ahead of print |
| Date Published: | 2023-01-01 |
| Online Publication Date: | 2023-01-01 |
| Language: | English |
| ACCESSION: | WOS:001038559900002 |
| DOI: | 10.1038/s41590-023-01572-4 |
| PROVIDER: | wos |
| Notes: | Article; Early Access -- Source: Wos |
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