Resolution of Inflammation

In a series of recent in vitro co-culture experiments, NK cells were shown to induce neutrophil apoptosis in a contact-dependent manner that required recognition of an as yet unidentified ligand on the neutrophil surface by the NK cell activatory receptor NKp46 [12]. This observation, combined with the ability of NK cells to lyse DCs and T cells via perforin-mediated cytotoxicity [13], suggests a role for NK cells in the resolution of inflammation.

Human ageing is associated with a reduced frequency of circulating NKp46+ NK cells [33,41]. Couple this change in surface phenotype to the reduced number of NK cells present at sites of inflammation in aged mice [36, 37], then it is conceivable to think that the rates of NK cell-mediated neutrophil apoptosis would be reduced in older adults, a consequence of which would be the slower resolution of inflammatory responses. Along similar lines, based on our data showing an age-related reduction in perforin secretion by activated NK cells [33] , one would predict that NKCC towards CD4+ T cells, which in the setting of viral infection has been proposed to prevent immune-mediated pathology [13], would also be reduced in older adults.

Away from NK cells, we recently provided ex vivo evidence that suggests ageing is associated with increased rates of neutrophil degranulation in the absence of infection [15]. Coinciding with elevated systemic neutrophil protease activity, this age-related increase in the function of unstimulated neutrophils may contribute to the chronic low-grade inflammatory state of older adults by triggering widespread collateral tissue damage [15].

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