<\/p>\n
\u00a0<\/strong>SACRE K1,2,3<\/sup>, Cl\u00e9ment M4<\/sup>, Charles N2,3<\/sup>, Escoubet B5<\/sup>, Guedj K4<\/sup>, Chauveheid MP1<\/sup>, Ollivier V4<\/sup>, Caligiuri G3,4<\/sup>, Nicoletti A3,4<\/sup>; Papo T1,2,3<\/sup><\/p>\n 1-Service de M\u00e9decine Interne, H\u00f4pital Bichat, Universit\u00e9 Paris Diderot, PRES Sorbonne Paris Cit\u00e9, Assistance Publique H\u00f4pitaux de Paris, Paris, France<\/p>\n 2-INSERM U1149, Universit\u00e9 Paris Diderot, Laboratoire d\u2019excellence INFLAMEX, PRES Sorbonne Paris Cit\u00e9, Paris, France<\/p>\n 3-D\u00e9partement Hospitalo-Universitaire FIRE (Fibrosis, Inflammation and Remodelling in Renal and Respiratory Diseases), Universit\u00e9 Paris Diderot, PRES Sorbonne Paris Cit\u00e9, Paris, France<\/p>\n 4-INSERM U1148, Universit\u00e9 Paris Diderot, PRES Sorbonne Paris Cit\u00e9, Paris, France<\/p>\n 5-D\u00e9partement de Physiologie, H\u00f4pital Bichat, Universit\u00e9 Paris Diderot, PRES Sorbonne Paris Cit\u00e9, Assistance Publique H\u00f4pitaux de Paris, Paris,\u00a0France<\/p>\n \u00a0karim.sacre@bch.aphp.fr<\/a><\/p>\n \u00a0Introduction<\/strong> Cardiovascular disease (CVD) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). As atherosclerosis is itself immune-mediated, specific features of SLE-associated immunity might explain accelerated cardiovascular disease in this population. We herein investigated the role of T cells and plasmacytoid dendritic cells (pDCs) – both crucial in SLE pathogenesis – in atherosclerosis associated with SLE.<\/p>\n \u00a0Results<\/strong> We first observed that peripheral CD4+<\/sup>T cells expressing CXCR3, a chemokine receptor involved in recruitment of T cells in atherosclerotic lesions, were high in SLE patients and correlated with atherosclerosis, as assessed by measurements of carotid internal carotid artery wall thickness (ICWT). Such CD4+<\/sup>CXCR3+<\/sup> T cells were antigen-primed and produced high levels of TNF-\u03b1. On the other hand, CXCR3 ligands (i.e. CXCL9, CXCL10, CXCL11) were high is SLE patients with active disease. In addition, IFN-\u03b1 produced by pDCs upon TLR-9 stimulation induced both the in vitro expansion of CD4+<\/sup>CXCR3+<\/sup> T cells and production of CXCR3 ligands by human coronary endothelial cells (HCEC). Eventually, TLR-9 stimulation 1-induced the development of anti-ssDNA autoantibodies and a significant rising of CXCL10 in serum, 2-enhanced CD4+<\/sup>CXCR3+<\/sup> T cells recruitment in arterial wall, and 3-promoted atheroslerosis in apoE-\/- mice.<\/p>\n \u00a0Conclusion<\/strong> SLE-associated atherosclerosis may be driven by a positive pathway in which IFN-\u03b1 produced by pDCS promotes the expansion of a high frequency of antigen-stimulated, CD4+<\/sup>CXCR3+<\/sup> T cells and induces endothelial cells to secrete CXCR3 ligands, which itself drive progressive infiltration of the arterial wall and atherosclerosis.<\/p>\n<\/p>\n <\/p>","protected":false},"excerpt":{"rendered":" CD4+CXCR3+ T cells and plasmacytoid dendritic cells enhanced atherosclerosis in patients with Systemic Lupus Erythematosus (SLE) \u00a0SACRE K1,2,3, Cl\u00e9ment M4, Charles N2,3, Escoubet B5, Guedj K4, Chauveheid MP1, Ollivier V4, Caligiuri G3,4, Nicoletti A3,4; Papo T1,2,3 1-Service de M\u00e9decine Interne, Lire la suite