TY  - JOUR
A1  - Erbel, Christian
A1  - Akhavanpoor, Mohammadreza
A1  - Okuyucu, Deniz
A1  - Wangler, Susanne
A1  - Dietz, Alex
A1  - Zhao, Li
A1  - Stellos, Konstantinos
A1  - Little, Kristina M.
A1  - Lasitschka, Felix
A1  - Doesch, Andreas
A1  - Hakimi, Maani
A1  - Dengler, Thomas J.
A1  - Giese, Thomas
A1  - Blessing, Erwin
A1  - Katus, Hugo
A1  - Gleissner, Christian A.
T1  - IL-17A influences essential functions of the monocyte/macrophage lineage and is involved in advanced murine and human atherosclerosis
T2  - The journal of immunology
N2  - Atherosclerosis is a chronic inflammatory disease. Lesion progression is primarily mediated by cells of the monocyte/macrophage lineage. IL-17A is a proinflammatory cytokine, which modulates immune cell trafficking and is involved inflammation in (auto)immune and infectious diseases. But the role of IL-17A still remains controversial. In the current study, we investigated effects of IL-17A on advanced murine and human atherosclerosis, the common disease phenotype in clinical care. The 26-wk-old apolipoprotein E–deficient mice were fed a standard chow diet and treated either with IL-17A mAb (n = 15) or irrelevant Ig (n = 10) for 16 wk. Furthermore, essential mechanisms of IL-17A in atherogenesis were studied in vitro. Inhibition of IL-17A markedly prevented atherosclerotic lesion progression (p = 0.001) by reducing inflammatory burden and cellular infiltration (p = 0.01) and improved lesion stability (p = 0.01). In vitro experiments showed that IL-17A plays a role in chemoattractance, monocyte adhesion, and sensitization of APCs toward pathogen-derived TLR4 ligands. Also, IL-17A induced a unique transcriptome pattern in monocyte-derived macrophages distinct from known macrophage types. Stimulation of human carotid plaque tissue ex vivo with IL-17A induced a proinflammatory milieu and upregulation of molecules expressed by the IL-17A–induced macrophage subtype. In this study, we show that functional blockade of IL-17A prevents atherosclerotic lesion progression and induces plaque stabilization in advanced lesions in apolipoprotein E–deficient mice. The underlying mechanisms involve reduced inflammation and distinct effects of IL-17A on monocyte/macrophage lineage. In addition, translational experiments underline the relevance for the human system.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/37178
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-371782
SN  - 1550-6606
SN  - 0022-1767
N1  - This article is distributed under The American Association of Immunologists, Inc., Reuse Terms and Conditions for Author Choice articles. http://www.jimmunol.org/site/misc/authorchoice.xhtml
VL  - 193
IS  - 9
SP  - 4344
EP  - 4355
PB  - American Association of Immunologists
CY  - Bethesda, Md.
ER  -