The IMMENSE Study: The Interplay Between iMMune and ENdothelial Cells in Mediating Cardiovascular Risk in Systemic Lupus Erythematosus
Patients with systemic lupus erythematosus (SLE) have a significant increase in cardiovascular (CV) risk although they display a preserved number of circulating angiogenic CD3 CD31 CXCR4 T cells (T ), a subpopulation of T cells which promotes repair of damaged endothelium. This happens due to the co...
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Published in | Frontiers in immunology Vol. 11; p. 572876 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
29.10.2020
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Subjects | |
Online Access | Get full text |
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Summary: | Patients with systemic lupus erythematosus (SLE) have a significant increase in cardiovascular (CV) risk although they display a preserved number of circulating angiogenic CD3
CD31
CXCR4
T cells (T
), a subpopulation of T cells which promotes repair of damaged endothelium. This happens due to the concomitant expansion of a T
subset with immunosenescent features, such as the loss of CD28. Therefore, the aim of this study was to elucidate the interplay between T
subpopulations and endothelial cells in a group of young SLE patients without previous cardiovascular events. Twenty SLE female patients and 10 healthy controls (HCs) were recruited. Flow cytometric analysis of endothelial progenitor cells (EPCs) and T
subsets were performed and serum levels of interleukin (IL)-6, -8, matrix metalloproteinase (MMP)-9 and interferon (IFN)-
were measured. Human umbilical vein endothelial cells (HUVECs) proliferation and pro-inflammatory phenotype in response to subjects' serum stimulation were also evaluated. Results showed that the percentage of T
and EPC subsets was reduced in SLE patients compared with HCs, with a marked increase of senescent CD28
cells among T
subset. SLE disease activity index-2000 (SLEDAI-2K) was inversed related to T
cells percentage. Furthermore, IL-8 serum levels were directly correlated with the percentage of T
and inversely related to the CD28
T
subsets. We indirectly evaluated the role of the T
subset on the endothelium upon stimulation with serum from subjects with a low percentage of T
CD3
cells in HUVECs. HUVECs displayed pro-inflammatory phenotype with up-regulation of mRNA for IL-6, intercellular adhesion molecule (ICAM)-1 and endothelial leukocyte adhesion molecule (ELAM)-1. Cell proliferation rate was directly related to IL-8 serum levels and EPC percentage. In highly selected young SLE patients without previous CV events, we found that the deterioration of T
compartment is an early event in disease course, preceding the development of an overt cardiovascular disease and potentially mediated by SLE-specific mechanisms. The overcome of the CD28
subset exerts detrimental role over the T
phenotype, where T
could exert an anti-inflammatory effect on endothelial cells and might orchestrate
IL-8 the function of EPCs, ultimately modulating endothelial proliferation rate. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors share senior authorship Reviewed by: Fabio Malavasi, University of Turin, Italy; Artur Augusto Paiva, Coimbra Hospital and University Center, Portugal These authors have contributed equally to this work Edited by: Marta Catalfamo, Georgetown University Medical Center, United States This article was submitted to T Cell Biology, a section of the journal Frontiers in Immunology |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2020.572876 |