Cross-talk between iNKT cells and monocytes triggers an atheroprotective immune response in SLE patients with asymptomatic plaque

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Science Immunology  02 Dec 2016:
Vol. 1, Issue 6, eaah4081
DOI: 10.1126/sciimmunol.aah4081

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Letting “SLE-P”ing plaques lie

Patients with the autoimmune disease systemic lupus erythematosus (SLE) are more likely to develop atherosclerosis than healthy individuals. Smith et al. hypothesized that invariant natural killer T (iNKT) cells contribute to this process because of their connection to both immune responses and lipids. They found that iNKT cells from SLE patients with asymptomatic plaque (SLE-P) produced more of the T helper 2 (TH2) cytokine interleukin-4 than those from SLE patients with no plaques. These SLE-P iNKT cells were associated with changes in lipid composition and monocyte skewing to the M2 phenotype. These data suggest that SLE-P iNKT cells may connect changes in lipids and the immune response, contributing to the development of cardiovascular disease in SLE patients.


Accelerated atherosclerosis is a complication of the autoimmune rheumatic disease systemic lupus erythematosus (SLE). We questioned the role played by invariant natural killer T (iNKT) cells in this process because they not only are defective in autoimmunity but also promote atherosclerosis in response to CD1d-mediated lipid antigen presentation. iNKT cells from SLE patients with asymptomatic plaque (SLE-P) had increased proliferation and interleukin-4 production compared with those from SLE patients with no plaque. The anti-inflammatory iNKT cell phenotype was associated with dyslipidemia and was driven by altered monocyte phospholipid expression and CD1d-mediated cross-talk between iNKT cells and monocytes but not B cells. Healthy iNKT cells differentiated in the presence of healthy monocytes and SLE-P serum polarized macrophages toward an anti-inflammatory M2 phenotype. Conversely, patients with clinical cardiovascular disease had unresponsive iNKT cells and increased proinflammatory monocytes. iNKT cell function could link immune responses, lipids, and cardiovascular disease in SLE patients and, together with serum lipid taxonomy, help predict preclinical atherosclerosis in SLE patients.

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