Smith, EC; (2016) The role of invariant Natural Killer T cells in SLE patients with atherosclerosis. Doctoral thesis , UCL (University College London).

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Abstract

Accelerated atherosclerosis is a complication of the rheumatic disease systemic lupus erythematosus (SLE). I questioned the role of invariant Natural Killer T (iNKT) cells in this process, since they are known to be defective in SLE but also promote atherosclerosis in response to CD1d-mediated lipid presentation. SLE patients with asymptomatic plaque (SLE-P) had an altered iNKT cell phenotype to those without plaque (SLE-NP), characterised by differences in activation marker expression and increased IL-4. This SLE-P iNKT cell phenotype correlated with differences in serum lipids including VLDL and coud be recapitulated in vitro by culturing healthy PBMCs with serum from SLE-P patients, an effect that was inhibited in the presence of anti-CD1d. Whilst differences in CD1d and lipid raft co-localisation and recycling were found in SLE patients, no difference was observed between SLE-NP and SLE-P patients. Isolation of phospholipids from SLE-P patients confirmed that differences in the lipids being presented were driving the anti-inflammatory iNKT cell phenotype in SLE-P patients. The finding that healthy iNKT cells, differentiated in the presence of healthy monocytes and serum from SLE-P patients, could induce THP-1 macrophage polarisation towards an anti-inflammatory M2-like phenotype suggested a protective role for iNKT cells in SLE patients with subclinical atherosclerosis. This was confirmed by studying a group of SLE patients who had suffered a cardiovascular event, where this protective iNKT cell phenotype seen in asymptomatic patients was lost.

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