Purpose Systemic lupus erythematosus (SLE) is associated with dyslipidemia and increased cardiovascular risk. The SLE pattern is characterised by high plasma levels of low-density lipoproteins (LDL) and triglycerides and low levels of high-density lipoproteins (HDL). HDL is a complex plasma lipoprotein that is recognised for its protective role in atherosclerotic disease. It consists of an outer layer of lipids and apolipoproteins, with apolipoproteinA-1 (apoA-1) constituting 70% of the protein content, a triglyceride and cholesterol ester-rich core, and several enzymes. In addition to its anti-atherogenic properties, mainly associated with reverse cholesterol transport from vessels, HDL has also anti-inflammatory properties that are not clearly understood. This work aims to show the effect of HDL on T lymphocyte proliferation.
Methods Peripheral blood mononuclear cells (PBMCs) were isolated from 7 SLE patients, with at least 4 SLICC/ACR classification criteria and normal serum lipid profiles, and 3 healthy donors. PBMCs were cultured with and without HDL (at the concentrations of 50, 300 and 600 µg/mL) before CD3 and CD28 stimulation. After 4 days in culture, T cell proliferation was measured by flow cytometry through Ki-67 staining. Regulator T cells (Tregs) phenotyping (CD4 +CD25+CD27-FoxP3+) was performed. The expression of the cholesterol transporter ABCA1 in T lymphocytes was also measured by flow cytometry.
Results HDL decreased T cell proliferation in a dose-dependent manner, with the biggest effect obtained with the physiologic concentration of 600 µg/mL. The inhibition of T cell proliferation was more pronounced in SLE patients than in the healthy donors. SLE patients tend to have higher baseline T cell proliferation measured by ki-67 expression. There were no differences in the prevalence of Tregs among patients and healthy donors. The expression of ABCA1 on the surface of T lymphocytes was similar between groups.
Conclusions This study is the first demonstration of a regulatory effect of HDL on the adaptive immune system of SLE patients. Here we show that HDL can decrease T cell proliferation, which is not correlated with the expression of the ABCA1, the main cholesterol transporter to ApoA-1. We expect to further elucidate HDL effects on the immune system in future studies.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.