Journal
JOURNAL OF CELL SCIENCE
Volume 134, Issue 7, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.258570
Keywords
Cellular activation; Cytotoxicity; Disease; Immune synapse; Mechanosensitivity; Natural killer cell
Categories
Funding
- Wellcome Trust Investigator Award [110091/Z/15/Z]
- Medical Research Council
- Manchester Collaborative Centre for Inflammation Research (GlaxoSmithKline)
- Manchester Collaborative Centre for Inflammation Research (AstraZeneca)
- Manchester Collaborative Centre for Inflammation Research (University of Manchester, UK)
- Wellcome Trust [110091/Z/15/Z] Funding Source: Wellcome Trust
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NK cells are more effectively stimulated to secrete various antibodies when encountering stiff targets compared to soft targets, which may impact NK cell recognition and response. Varying target stiffness can alter the mechanosensitivity of immune synapses, highlighting soft targets as a blind spot in NK cell recognition.
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 IFN gamma, by stiff (142 kPa) compared to soft (1 kPa) planar substrates. To create surrogate spherical targets of defined stiffness, sodium alginate was used to synthesise soft (9 kPa), medium (34 kPa) or stiff (254 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.
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