Chan A et al. - The interaction of natural killer (NK) cells with fibroblast-like synoviocytes (FLS) results in increased IL-15 expression and the production of proinflammatory chemokines, cytokines, and MMPs, which may contribute to joint inflammation. Methods
Aim was to determine whether the interaction between NK cells and FLS from spondylarthritis (SpA) pts results in a proinflammatory response
Autologous NK cells and FLS were obtained from 6 pts with SpA, 4 pts with RA and 8 pts with OA
Physical interactions between NK cells and FLS were studied by time-lapse phase-contrast microscopy
FACS analysis was used to study the activation, proliferation, and survival of NK cells in contact with FLS
Cytokine and stromal factor production were measured by a multiple cytokine bead assay
Results
NK cells both adhered to and migrated beneath the FLS monolayer
FLS from SpA and RA pts supported increased pseudoemperipolesis, activation, cytokine production, and survival of NK cells
The production of proinflammatory cytokines, including IL-6, IL-8, IL-1 &beta , and IL-15, was increased in cocultures of NK cells and FLS
Production of interferon- &gamma, RANTES, and matrix metalloproteinase 3 (MMP-3) by NK cell and FLS coculture was greatest in SpA patients
Surface expression of IL-15 on FLS increased in SpA and RA pts, but not OA pts
Blockade with an IL-15 monoclonal antibody resulted in increased apoptosis of NK cells
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