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(Circulation. 2007;116:1707-1713.)
© 2007 American Heart Association, Inc.

Vascular Medicine

Measles Virus Nucleoprotein Induces a Regulatory Immune Response and Reduces Atherosclerosis in Mice

Hafid Ait-Oufella, MD; Branka Horvat, PhD; Yann Kerdiles, PhD; Olivier Herbin, MSc; Pierre Gourdy, MD, PhD; Jamila Khallou-Laschet, MSc; Régine Merval;; Bruno Esposito;; Alain Tedgui, PhD; Ziad Mallat, MD, PhD

From Inserm U689, Centre de Recherche Cardiovasculaire Lariboisière, Hôpital Lariboisière, Paris (H.A.-O., O.H., R.M., B.E., A.T., Z.M.); Inserm U758 and Ecole Normale Supérieure de Lyon, IFR128 BioSciences, Lyon (B.H., Y.K.); Inserm U589, IFR 31, CHU Toulouse-Rangueil, Toulouse (P.G.); and Inserm UMRS 872, Centre de Recherche des Cordeliers, Paris (J.K.-L.), France.

Correspondence to Ziad Mallat, MD, PhD, Inserm U689, Centre de Recherche Cardiovasculaire Lariboisière, Hôpital Lariboisière, 41, Bd de la Chapelle, 75010 Paris, France. E-mail mallat{at}larib.inserm.fr

Received February 27, 2007; Accepted July 29, 2007.

Background— Recent studies clearly suggest that regulatory T cells play a critical role in the control of the immunoinflammatory response in atherosclerosis and substantially limit lesion development. Measles virus infection or vaccination is associated with immune depression, in part through the induction of an antiinflammatory response by measles virus nucleoprotein. We hypothesized that the antiinflammatory properties of measles virus nucleoprotein may limit the development atherosclerosis.

Methods and Results— Here, we show for the first time that repetitive administration of measles virus nucleoprotein to apolipoprotein E–deficient mice promotes an antiinflammatory T-regulatory-cell type 1–like response and inhibits macrophage and T-cell accumulation within the lesions. Treatment with measles virus nucleoprotein significantly reduces the development of new atherosclerotic plaques and markedly inhibits the progression of established lesions. The antiatherosclerotic potential of nucleoprotein is retained in its short N-terminal segment. The protective effects on lesion size are lost in mice with lymphocyte deficiency.

Conclusions— Our findings identify a novel mechanism of immune modulation by measles virus nucleoprotein through the promotion of a regulatory T-cell response and suggest that this property may be harnessed for treating atherosclerosis, the first cause of heart disease and stroke.

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