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M. Benagiano et al.
artery diseases.45 Expression of IL-17 in human atheroscle- rotic lesions is associated with increased inflammation and plaque vulnerability, and increased Th17 cells.46 An increased incidence of atherosclerosis associated with peripheral blood Th17 responses has been demonstrated in patients with SLE.47
IFN-g and IL-17. Thus, it is possible to speculate that Th17 and Th1 cells co-migrate to the inflamed tissue and co- operate in the ongoing inflammatory process within the atherosclerotic lesion.16,17,39,52
In addition, upon appropriate Ag stimulation, the major- ity of atherosclerotic plaque-derived β2GPI-specific clones induced both perforin-mediated cytolysis and Fas/FasL- mediated apoptosis in target cells and were able to drive the upregulation of TF production by monocytes within ather- osclerotic plaques, thus further contributing to the throm- bogenicity of lesions.42,43,53 Our results demonstrate that β2GPI is a major factor able to drive Th17 and Th1 inflam- matory process in SLE-APS atherosclerosis, and suggest that Th17/Th1 cell pathway and β2GPI may represent impor- tant targets for the prevention and treatment of the disease.
Funding
This research has been supported by grants from Italian Ministry of University and Research and Italian Ministry of Health (MMDE), IRCCS Istituto Auxologico Italiano, Ricerca Corrente (PLM).
We have demonstrated that β2GPI was able to activate Th17 and Th1 responses in atherosclerotic lesions of SLE- APS patients. The relevance of Th17/Th1 cells in non-SLE- atherosclerosis patients have been demonstrated in other studies,48,49 suggesting that Th1 and Th17 cells might plas- tically shift into each other in different phases of the dis- ease. It has been shown that Th17 cells might shift towards Th1 but not to Th2 via IL-12 receptor signaling.50
Overall, our findings support the concept that a crucial component of atherosclerosis in SLE-APS is represented by T-cell-mediated immunity and that chronic Th response against β2GPI plays an important role in the genesis of atheroma in SLE-APS patients.51 Among β2GPI- specific IL-17–producing Th cells, the majority were polar- ized Th17 cells, whereas others were able to produce both
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