Natural killer cell immune synapse formation and cytotoxicity are controlled by tension of the target interface.
J Cell Sci
; 134(7)2021 04 01.
Article
em En
| MEDLINE
| ID: mdl-33712452
ABSTRACT
Natural killer (NK) cells can kill infected or transformed cells via a lytic immune synapse. Diseased cells may exhibit altered mechanical properties but how this impacts NK cell responsiveness is unknown. We report that human NK cells were stimulated more effectively to secrete granzymes A and B, FasL (also known as FasLG), granulysin and IFNγ, by stiff (142â
kPa) compared to soft (1â
kPa) planar substrates. To create surrogate spherical targets of defined stiffness, sodium alginate was used to synthesise soft (9â
kPa), medium (34â
kPa) or stiff (254â
kPa) cell-sized beads, coated with antibodies against activating receptor NKp30 (also known as NCR3) and the integrin LFA-1 (also known as ITGAL). Against stiff beads, NK cells showed increased degranulation. Polarisation of the microtubule-organising centre and lytic granules were impaired against soft targets, which instead resulted in the formation of unstable kinapses. Thus, by varying target stiffness to characterise the mechanosensitivity of immune synapses, we identify soft targets as a blind spot in NK cell recognition. This article has an associated First Person interview with the co-first authors of the paper.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Centro Organizador dos Microtúbulos
Limite:
Humans
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Reino Unido