Attenuated atherosclerosis upon IL-17R signaling disruption in LDLr deficient mice.
Atherosclerosis is an inflammatory disease characterized by the influx of macrophages and T cells and IL-17 may connect innate and adaptive immune responses involved in atherogenesis. We investigated the role of IL-17 receptor signaling in atherosclerosis and transplanted LDLr deficient recipient mice with IL-17R deficient bone marrow. Induction of atherosclerosis by Western-type diet induced a 46% reduction in lesion size in the aortic root and the plaque composition revealed no significant changes in collagen content and neutrophil counts, but a reduction in mast cell number and an increase in macrophage number. In addition, we observed a decrease in anti-oxLDL antibodies of the IgG class upon IL-17R BMT, while introduction of IL-17R deficient bone marrow resulted in a reduced IL-6 production and an increased IL-10 production. In conclusion, signaling via the IL-17 receptor in bone marrow derived cells enhances the process of atherosclerosis.
van Es
T
T
Division of Biopharmaceutics, Leiden Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
van Puijvelde
G H M
GH
Ramos
O H
OH
Segers
F M E
FM
Joosten
L A
LA
van den Berg
W B
WB
Michon
I M
IM
de Vos
P
P
van Berkel
Th J C
TJ
Kuiper
J
J
D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000601:surgery; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000379:methods; D008077:Lipoproteins, LDL / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000276:immunology*; D011973:Receptors, LDL / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction
D001323:Autoantibodies; D008077:Lipoproteins, LDL; D053722:Receptors, Interleukin-17; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein