title: CD4+CXCR3+ T cells and plasmacytoid dendritic cells drive accelerated atherosclerosis associated with systemic lupus erythematosus.
abstract: Cardiovascular disease due to accelerated atherosclerosis is the leading cause of death in patients with systemic lupus erythematosus (SLE). Noteworthy, accelerated atherosclerosis in SLE patients appears to be independant of classical Framingham risk factors. This suggests that aggravated atherosclerosis in SLE patients may be a result of increased inflammation and altered immune responses. However, the mechanisms that mediate the acceleration of atherosclerosis in SLE remain elusive. Based on experimental data which includes both humans (SLE patients and control subjects) and rodents (ApoE-/- mice), we herein propose a multi-step model in which the immune dysfunction associated with SLE (i.e. high level of IFN-α production by TLR 9-stimulated pDCs) is associated with, first, an increased frequency of circulating pro inflammatory CD4+CXCR3+ T cells; second, an increased production of CXCR3 ligands by endothelial cells; third, an increased recruitment of pro-inflammatory CD4+CXCR3+ T cells into the arterial wall, and fourth, the development of atherosclerosis. In showing how SLE may promote accelerated atherosclerosis, our model also points to hypotheses for potential interventions, such as pDCs-targeted therapy, that might be studied in the future.
authors.affiliation: INSERM U1148, Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Clement
authors.affiliation: INSERM U1149, Université Paris Diderot, Laboratoire d'excellence INFLAMEX, PRES Sorbonne Paris Cité, Paris, France; Département Hospitalo-Universitaire FIRE (Fibrosis, Inflammation and Remodelling in Renal and Respiratory Diseases), Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Charles
authors.affiliation: Département de Physiologie, Hôpital Bichat, Université Paris Diderot, PRES Sorbonne Paris Cité, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Escoubet
authors.affiliation: INSERM U1148, Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Guedj
authors.affiliation: Département de Médecine Interne, Hôpital Bichat, Université Paris Diderot, PRES Sorbonne Paris Cité, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Chauveheid
authors.affiliation: INSERM U1148, Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France; Département Hospitalo-Universitaire FIRE (Fibrosis, Inflammation and Remodelling in Renal and Respiratory Diseases), Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Caligiuri
authors.affiliation: INSERM U1148, Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France; Département Hospitalo-Universitaire FIRE (Fibrosis, Inflammation and Remodelling in Renal and Respiratory Diseases), Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Antonino
authors.initials: A
authors.lastname: Nicoletti
authors.affiliation: INSERM U1149, Université Paris Diderot, Laboratoire d'excellence INFLAMEX, PRES Sorbonne Paris Cité, Paris, France; Département Hospitalo-Universitaire FIRE (Fibrosis, Inflammation and Remodelling in Renal and Respiratory Diseases), Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France; Département de Médecine Interne, Hôpital Bichat, Université Paris Diderot, PRES Sorbonne Paris Cité, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Papo
authors.affiliation: INSERM U1149, Université Paris Diderot, Laboratoire d'excellence INFLAMEX, PRES Sorbonne Paris Cité, Paris, France; Département Hospitalo-Universitaire FIRE (Fibrosis, Inflammation and Remodelling in Renal and Respiratory Diseases), Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France; Département de Médecine Interne, Hôpital Bichat, Université Paris Diderot, PRES Sorbonne Paris Cité, Assistance Publique Hôpitaux de Paris, Paris, France. Electronic address: karim.sacre@bch.aphp.fr.
authors.forename: Karim
authors.initials: K
authors.lastname: Sacre
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D054367:Receptors, CXCR3
chemical_list: C515187:CXCR3 protein, human; D054367:Receptors, CXCR3
keywords: Accelerated atherosclerosis; CXCR3+CD4+ T cells; Chemokines; Lupus; Plasmacytoid dendritic cells