Angiogenic T cell expansion correlates with severity of peripheral vascular damage in systemic sclerosis

Abstract

The mechanisms underlying endothelial cell injury and defective vascular repair in systemic sclerosis (SSc) remain unclear. Since the recently discovered angiogenic T cells (Tang) may have an important role in the repair of damaged endothelium, this study aimed to analyze the Tang population in relation to disease-related peripheral vascular features in SSc patients. Tang (CD3+CD31+CXCR4+) were quantified by flow cytometry in peripheral blood samples from 39 SSc patients and 18 healthy controls (HC). Circulating levels of the CXCR4 ligand stromal cell-derived factor (SDF)-1α and proangiogenic factors were assessed in paired serum samples by immunoassay. Serial skin sections from SSc patients and HC were subjected to CD3/CD31 and CD3/CXCR4 double immunofluorescence. Circulating Tang were significantly increased in SSc patients with digital ulcers (DU) compared either with SSc patients without DU or with HC. Tang levels were significantly higher in SSc patients with late nailfold videocapillaroscopy (NVC) pattern than in those with early/active NVC patterns and in HC. No difference in circulating Tang was found when comparing either SSc patients without DU or patients with early/active NVC patterns and HC. In SSc peripheral blood, Tang percentage was inversely correlated to levels of SDF-1α and CD34+CD133+VEGFR-2+ endothelial progenitor cells (EPC), and positively correlated to levels of vascular endothelial growth factor and matrix metalloproteinase-9. Tang were frequently detected in SSc dermal perivascular inflammatory infiltrates. In summary, our findings demonstrate for the first time that Tang cells are selectively expanded in the circulation of SSc patients displaying severe peripheral vascular complications like DU. In SSc, Tang may represent a potentially useful biomarker reflecting peripheral vascular damage severity. Tang expansion may be an ineffective attempt to compensate the need for increased angiogenesis and EPC function. Further studies are required to clarify the function of Tang cells and investigate the mechanisms responsible for their change in SSc.

The IMMENSE Study: The Interplay Between iMMune and ENdothelial Cells in Mediating Cardiovascular Risk in Systemic Lupus Erythematosus

“…The IMMENSE study provides novel insights into the evaluation of CV subclinical alterations in SLE by unveiling some potential aspects of the complex interplay between T ang , EPCs, and endothelial cells. The focus of the study was on circulating T ang cells, which were recently demonstrated to be a potentially useful biomarker reflecting vascular alterations in CV and autoimmune diseases (10,11,32,33). In our highly selected young SLE patients without previous CV events and a low rate of traditional CV risk-factors, we found a mild decrease of T ang cells in patients in comparison with HCs, confirming our previous observation (34).…”

The immunopathogenesis of fibrosis in systemic sclerosis

“…In addition, a more recent study has confirmed that Th2 and Th17 cells are found in higher frequencies in SSc patients, and this was found to positively correlate with IL-35 levels, although a causal link has not been established [58]. Further evidence of disruption to T cell homeostasis comes from a recent study showing that SSc patients displaying severe peripheral vascular complications have an expansion of the recently discovered angiogenic T cells [59]. This expansion in angiogenic T cells may also demonstrate a link between immune cell activation and vasculopathy in SSc.…”

The Role of Endothelial Progenitors in the Repair of Vascular Damage in Systemic Sclerosis

“…In SSc, Tang cell counts have been reported to be selectively increased in the PB of SSc patients with severe vascular complications like digital ulcers and there was an inverse correlation between circulating Tang and EPCs (defined as CD34 + CD133 + VEGFR2 + ). Furthermore, the presence of circulating Tang cells positively correlated with the levels of pro-angiogenic factors, namely VEGF and MMP-9 ( 56 ). Such Tang cell expansion has, therefore, been suggested as a possible ineffective attempt to compensate the decrease in EPC number ( 56 ).…”

“…Furthermore, the presence of circulating Tang cells positively correlated with the levels of pro-angiogenic factors, namely VEGF and MMP-9 ( 56 ). Such Tang cell expansion has, therefore, been suggested as a possible ineffective attempt to compensate the decrease in EPC number ( 56 ).…”