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Titel: PIEZO1-mediated mechanosensing governs NK-cell killing efficiency and infiltration in three-dimensional matrices
VerfasserIn: Yanamandra, Archana K.
Zhang, Jingnan
Montalvo, Galia
Zhou, Xiangda
Biedenweg, Doreen
Zhao, Renping
Sharma, Shulagna
Hoth, Markus
Lautenschläger, Franziska
Otto, Oliver
del Campo, Aránzazu
Qu, Bin
Sprache: Englisch
Titel: European Journal of Immunology
Bandnummer: 54
Heft: 3
Verlag/Plattform: Wiley
Erscheinungsjahr: 2024
Freie Schlagwörter: 3D matrices
Killing efficiency
Mechanosensing
NK cells
PIEZO1
DDC-Sachgruppe: 500 Naturwissenschaften
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Natural killer (NK) cells play a vital role in eliminating tumorigenic cells. Efficient locating and killing of target cells in complex three-dimensional (3D) environments are critical for their functions under physiological conditions. However, the role of mechanosensing in regulating NK-cell killing efficiency in physiologically relevant scenarios is poorly understood. Here, we report that the responsiveness of NK cells is regulated by tumor cell stiffness. NK-cell killing efficiency in 3D is impaired against softened tumor cells, whereas it is enhanced against stiffened tumor cells. Notably, the durations required for NK-cell killing and detachment are significantly shortened for stiffened tumor cells. Furthermore, we have identified PIEZO1 as the predominantly expressed mechanosensitive ion channel among the examined candidates in NK cells. Perturbation of PIEZO1 abolishes stiffness-dependent NK-cell responsiveness, significantly impairs the killing efficiency of NK cells in 3D, and substantially reduces NK-cell infiltration into 3D collagen matrices. Conversely, PIEZO1 activation enhances NK killing efficiency as well as infiltration. In conclusion, our findings demonstrate that PIEZO1-mediated mechanosensing is crucial for NK killing functions, highlighting the role of mechanosensing in NK-cell killing efficiency under 3D physiological conditions and the influence of environmental physical cues on NK-cell functions.
DOI der Erstveröffentlichung: 10.1002/eji.202350693
URL der Erstveröffentlichung: https://doi.org/10.1002/eji.202350693
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-419076
hdl:20.500.11880/37487
http://dx.doi.org/10.22028/D291-41907
ISSN: 1521-4141
0014-2980
Datum des Eintrags: 16-Apr-2024
Bezeichnung des in Beziehung stehenden Objekts: Supporting Information
In Beziehung stehendes Objekt: https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Feji.202350693&file=eji5670-sup-0001-Movie1.mp4
https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Feji.202350693&file=eji5670-sup-0002-Movie2.mp4
https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Feji.202350693&file=eji5670-sup-0003-Movie3.mp4
https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Feji.202350693&file=eji5670-sup-0004-Movie4.mp4
https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Feji.202350693&file=eji5670-sup-0005-Movie5.mp4
https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Feji.202350693&file=eji5670-sup-0006-Movie6.mp4
https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Feji.202350693&file=eji5670-sup-0007-SuppMat.pdf
Fakultät: M - Medizinische Fakultät
NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: M - Biophysik
NT - Chemie
NT - Physik
Professur: M - Prof. Dr. Markus Hoth
NT - Prof. Dr. Aránzazu del Campo
NT - Jun.-Prof. Dr. Franziska Lautenschläger
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes



Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons