Natural killer (NK) cells are a main subset of innate lymphocytes that contribute to host immune protection against viruses and tumors by mediating target cell killing and secreting a wide array of cytokines. Their functions are finely regulated by a balance between activating and inhibitory receptors and involve also adhesive interactions. Mechanotransduction is the process in which physical forces sensed by mechanosensors are translated into chemical signaling. Herein, we report findings on the involvement of this mechanism that is mainly mediated by actin cytoskeleton, in the regulation of NK cell adhesion, migration, tissue infiltration and functions. Actin represents the structural basis for NK cell immunological synapse (NKIS) and polarization of secretory apparatus. NK-target cell interaction involves the formation of both uropods and membrane nanotubes that allow target cell interaction over long distances. Actin retrograde flow (ARF) regulates NK cell signaling and controls the equilibrium between activation versus inhibition. Activating NKIS is associated with rapid lamellipodial ARF, whereas lower centripetal actin flow is present during inhibitory NKIS where β actin can associate with the tyrosine phosphatase SHP-1. Overall, a better knowledge of mechanotransduction might represent a future challenge: Realization of nanomaterials tailored for NK cells, would be important to translate in vitro studies in in vivo new immunotherapeutic approaches.

Mechanosensation and mechanotransduction in Natural Killer cells / Santoni, G.; Amantini, C.; Santoni, M.; Maggi, F.; Morelli, M. B.; Santoni, A.. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 12:(2021). [10.3389/fimmu.2021.688918]

Mechanosensation and mechanotransduction in Natural Killer cells

Maggi F.;Morelli M. B.;Santoni A.
2021

Abstract

Natural killer (NK) cells are a main subset of innate lymphocytes that contribute to host immune protection against viruses and tumors by mediating target cell killing and secreting a wide array of cytokines. Their functions are finely regulated by a balance between activating and inhibitory receptors and involve also adhesive interactions. Mechanotransduction is the process in which physical forces sensed by mechanosensors are translated into chemical signaling. Herein, we report findings on the involvement of this mechanism that is mainly mediated by actin cytoskeleton, in the regulation of NK cell adhesion, migration, tissue infiltration and functions. Actin represents the structural basis for NK cell immunological synapse (NKIS) and polarization of secretory apparatus. NK-target cell interaction involves the formation of both uropods and membrane nanotubes that allow target cell interaction over long distances. Actin retrograde flow (ARF) regulates NK cell signaling and controls the equilibrium between activation versus inhibition. Activating NKIS is associated with rapid lamellipodial ARF, whereas lower centripetal actin flow is present during inhibitory NKIS where β actin can associate with the tyrosine phosphatase SHP-1. Overall, a better knowledge of mechanotransduction might represent a future challenge: Realization of nanomaterials tailored for NK cells, would be important to translate in vitro studies in in vivo new immunotherapeutic approaches.
2021
cytotoxicity; immunological synapse; mechanosensation; mechanotransduction; natural killer (NK) cells
01 Pubblicazione su rivista::01g Articolo di rassegna (Review)
Mechanosensation and mechanotransduction in Natural Killer cells / Santoni, G.; Amantini, C.; Santoni, M.; Maggi, F.; Morelli, M. B.; Santoni, A.. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 12:(2021). [10.3389/fimmu.2021.688918]
File allegati a questo prodotto
File Dimensione Formato  
Santoni_Natural-killer-cells_2021.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 5.94 MB
Formato Adobe PDF
5.94 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1617297
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 14
social impact