TY - JOUR
T1 - The IMMENSE Study
T2 - The Interplay Between iMMune and ENdothelial Cells in Mediating Cardiovascular Risk in Systemic Lupus Erythematosus
AU - Bortoluzzi, Alessandra
AU - Chighizola, Cecilia Beatrice
AU - Fredi, Micaela
AU - Raschi, Elena
AU - Bodio, Caterina
AU - Privitera, Daniela
AU - Gonelli, Arianna
AU - Silvagni, Ettore
AU - Govoni, Marcello
AU - Cavazzana, Ilaria
AU - Airò, Paolo
AU - Meroni, Pier Luigi
AU - Tincani, Angela
AU - Franceschini, Franco
AU - Piantoni, Silvia
AU - Casciano, Fabio
N1 - Funding Information:
This work was supported by a grant from Fondazione Italiana per la Ricerca sull'Artrite (FIRA Onlus) and University of Ferrara (FAR 2020 N-FAR.L-BA_003).
Publisher Copyright:
© Copyright © 2020 Bortoluzzi, Chighizola, Fredi, Raschi, Bodio, Privitera, Gonelli, Silvagni, Govoni, Cavazzana, Airò, Meroni, Tincani, Franceschini, Piantoni and Casciano.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/29
Y1 - 2020/10/29
N2 - 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 (Tang), a subpopulation of T cells which promotes repair of damaged endothelium. This happens due to the concomitant expansion of a Tang subset with immunosenescent features, such as the loss of CD28. Therefore, the aim of this study was to elucidate the interplay between Tang 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 Tang subsets were performed and serum levels of interleukin (IL)-6, -8, matrix metalloproteinase (MMP)-9 and interferon (IFN)-γ 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 Tang and EPC subsets was reduced in SLE patients compared with HCs, with a marked increase of senescent CD28null cells among Tang subset. SLE disease activity index-2000 (SLEDAI-2K) was inversed related to Tang cells percentage. Furthermore, IL-8 serum levels were directly correlated with the percentage of Tang and inversely related to the CD28null Tang subsets. We indirectly evaluated the role of the Tang subset on the endothelium upon stimulation with serum from subjects with a low percentage of Tang 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 Tang 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 CD28null subset exerts detrimental role over the Tang phenotype, where Tang could exert an anti-inflammatory effect on endothelial cells and might orchestrate via IL-8 the function of EPCs, ultimately modulating endothelial proliferation rate.
AB - 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 (Tang), a subpopulation of T cells which promotes repair of damaged endothelium. This happens due to the concomitant expansion of a Tang subset with immunosenescent features, such as the loss of CD28. Therefore, the aim of this study was to elucidate the interplay between Tang 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 Tang subsets were performed and serum levels of interleukin (IL)-6, -8, matrix metalloproteinase (MMP)-9 and interferon (IFN)-γ 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 Tang and EPC subsets was reduced in SLE patients compared with HCs, with a marked increase of senescent CD28null cells among Tang subset. SLE disease activity index-2000 (SLEDAI-2K) was inversed related to Tang cells percentage. Furthermore, IL-8 serum levels were directly correlated with the percentage of Tang and inversely related to the CD28null Tang subsets. We indirectly evaluated the role of the Tang subset on the endothelium upon stimulation with serum from subjects with a low percentage of Tang 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 Tang 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 CD28null subset exerts detrimental role over the Tang phenotype, where Tang could exert an anti-inflammatory effect on endothelial cells and might orchestrate via IL-8 the function of EPCs, ultimately modulating endothelial proliferation rate.
KW - angiogenic T cells
KW - cardiovascular risk
KW - endothelial progenitor cells
KW - immunosenescence
KW - systemic lupus erythematosus
UR - http://www.scopus.com/inward/record.url?scp=85095990808&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85095990808&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2020.572876
DO - 10.3389/fimmu.2020.572876
M3 - Article
C2 - 33193356
AN - SCOPUS:85095990808
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 572876
ER -