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The Dendritic Cell Receptor DNGR-1 Promotes the Development of Atherosclerosis in Mice.
Haddad, Yacine; Lahoute, Charlotte; Clément, Marc; Laurans, Ludivine; Metghalchi, Sarvenaz; Zeboudj, Lynda; Giraud, Andreas; Loyer, Xavier; Vandestienne, Marie; Wain-Hobson, Julien; Esposito, Bruno; Potteaux, Stephane; Ait-Oufella, Hafid; Tedgui, Alain; Mallat, Ziad; Taleb, Soraya.
Afiliação
  • Haddad Y; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Lahoute C; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Clément M; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Laurans L; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Metghalchi S; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Zeboudj L; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Giraud A; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Loyer X; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Vandestienne M; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Wain-Hobson J; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Esposito B; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Potteaux S; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Ait-Oufella H; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Tedgui A; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Mallat Z; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
  • Taleb S; From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, Université Paris-Descartes, France (Y.H., C.L., L.L., S.M., L.Z., A.G., X.L., M.V., J.W.-H., B.E., S.P., H.A.-O., A.T., Z.M., S.T.); and Division of Cardiovascular Medicine, U
Circ Res ; 121(3): 234-243, 2017 Jul 21.
Article em En | MEDLINE | ID: mdl-28607102
ABSTRACT
RATIONALE Necrotic core formation during the development of atherosclerosis is associated with a chronic inflammatory response and promotes accelerated plaque development and instability. However, the molecular links between necrosis and the development of atherosclerosis are not completely understood. Clec9a (C-type lectin receptor) or DNGR-1 (dendritic cell NK lectin group receptor-1) is preferentially expressed by the CD8α+ subset of dendritic cells (CD8α+ DCs) and is involved in sensing necrotic cells. We hypothesized that sensing of necrotic cells by DNGR-1 plays a determinant role in the inflammatory response of atherosclerosis.

OBJECTIVE:

We sought to address the impact of total, bone marrow-restricted, or CD8α+ DC-restricted deletion of DNGR-1 on atherosclerosis development. METHODS AND

RESULTS:

We show that total absence of DNGR-1 in Apoe (apolipoprotein e)-deficient mice (Apoe-/-) and bone marrow-restricted deletion of DNGR-1 in Ldlr (low-density lipoprotein receptor)-deficient mice (Ldlr-/-) significantly reduce inflammatory cell content within arterial plaques and limit atherosclerosis development in a context of moderate hypercholesterolemia. This is associated with a significant increase of the expression of interleukin-10 (IL-10). The atheroprotective effect of DNGR-1 deletion is completely abrogated in the absence of bone marrow-derived IL-10. Furthermore, a specific deletion of DNGR-1 in CD8α+ DCs significantly increases IL-10 expression, reduces macrophage and T-cell contents within the lesions, and limits the development of atherosclerosis.

CONCLUSIONS:

Our results unravel a new role of DNGR-1 in regulating vascular inflammation and atherosclerosis and potentially identify a new target for disease modulation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Dendríticas / Receptores Imunológicos / Interleucina-10 / Lectinas Tipo C / Aterosclerose Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Circ Res Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Dendríticas / Receptores Imunológicos / Interleucina-10 / Lectinas Tipo C / Aterosclerose Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Circ Res Ano de publicação: 2017 Tipo de documento: Article