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The role of CLEC9a in atherosclerosis development
UntitledBook1.book Page 184 Monday, March 20, 2017 2:28 PM
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Archives of Cardiovascular Diseases Supplements (2017) 9, 183-184
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HFD (– 40%, p=0,0017), as compared to mice transplanted with wild-type bone marrow-derived cells. However, no effect of CLEC9A was observed after 13 weeks of HFD (p=0,4996), suggesting early effect of CLEC9A on atherosclerosis development.
The role of CLEC9a in atherosclerosis development Y. Haddad*, L. Laurans, S. Metghalchi, Z. Zeboudj, A. Giraud, Z. Mallat, S. Taleb UMR-970, INSERM, Paris, France *Corresponding author: [email protected] Necrotic core formation during the development of atherosclerosis is associated with a chronic inflammatory response and promotes accelerated plaque development and instability. We hypothesized that sensing of necrotic cells by CLEC9A, a C-type lectin receptors selectively expressed by the CD8α+ subset of dendritic cells (CD8α+DCs), plays a determinant role in the inflammatory response of atherosclerosis. Reconstitution of lethally-irradiated Ldlr-/- with bone marrow from CLEC9A-/- mice significantly reduced atherosclerotic lesion size in aortic root after 5 weeks of high fat diet (HFD) (– 45%, p=0,0059) and after 7 weeks of
© Elsevier Masson SAS. All rights reserved.
The same phenotype was observed in 20-week-old Apoe-/-CLEC9A-/compared to Apoe-/- mice put on chow diet (– 50%, p=0,0022). Interestingly, an increase of IL-10 expression (+60%, p=0,0093) was observed in spleens of mice deficient for CLEC9A. Furthermore, the beneficial effect observed in CLEC9A-/- was abolished in CLEC9A-/-IL-10-/- compared to IL-10/- (p=0,4452). Moreover, a specific deletion of Clec9a in CD8α+DC cells significantly increases Il10 expression, reduces macrophage and T cell contents within the lesions, and significantly limits the development of atherosclerosis. Our results identify a new role of Clec9a in regulating vascular inflammation and atherosclerosis development and potentially identify a new target for disease modulation. The author hereby declares no conflict of interest
184
Archives of Cardiovascular Diseases Supplements (2017) 9, 183-184
500
HFD (– 40%, p=0,0017), as compared to mice transplanted with wild-type bone marrow-derived cells. However, no effect of CLEC9A was observed after 13 weeks of HFD (p=0,4996), suggesting early effect of CLEC9A on atherosclerosis development.
The role of CLEC9a in atherosclerosis development Y. Haddad*, L. Laurans, S. Metghalchi, Z. Zeboudj, A. Giraud, Z. Mallat, S. Taleb UMR-970, INSERM, Paris, France *Corresponding author: [email protected] Necrotic core formation during the development of atherosclerosis is associated with a chronic inflammatory response and promotes accelerated plaque development and instability. We hypothesized that sensing of necrotic cells by CLEC9A, a C-type lectin receptors selectively expressed by the CD8α+ subset of dendritic cells (CD8α+DCs), plays a determinant role in the inflammatory response of atherosclerosis. Reconstitution of lethally-irradiated Ldlr-/- with bone marrow from CLEC9A-/- mice significantly reduced atherosclerotic lesion size in aortic root after 5 weeks of high fat diet (HFD) (– 45%, p=0,0059) and after 7 weeks of
© Elsevier Masson SAS. All rights reserved.
The same phenotype was observed in 20-week-old Apoe-/-CLEC9A-/compared to Apoe-/- mice put on chow diet (– 50%, p=0,0022). Interestingly, an increase of IL-10 expression (+60%, p=0,0093) was observed in spleens of mice deficient for CLEC9A. Furthermore, the beneficial effect observed in CLEC9A-/- was abolished in CLEC9A-/-IL-10-/- compared to IL-10/- (p=0,4452). Moreover, a specific deletion of Clec9a in CD8α+DC cells significantly increases Il10 expression, reduces macrophage and T cell contents within the lesions, and significantly limits the development of atherosclerosis. Our results identify a new role of Clec9a in regulating vascular inflammation and atherosclerosis development and potentially identify a new target for disease modulation. The author hereby declares no conflict of interest