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Cell Metab. 2019 Feb 5;29(2):475-487.e7. doi: 10.1016/j.cmet.2018.10.006. Epub 2018 Nov 8.

Interleukin-17 Drives Interstitial Entrapment of Tissue Lipoproteins in Experimental Psoriasis.

Author information

1
Department of Pathology & Immunology, Washington University, St Louis, MO 63110, USA.
2
Department of Cell Biology, Washington University, St Louis, MO 63110, USA.
3
Division of Dermatology, Department of Medicine, Washington University, St Louis, MO 63110, USA.
4
Institute for Molecular Engineering, University of Chicago, Chicago, IL 60637, USA.
5
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen 5009, Norway.
6
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
7
Department of Medicine, Division of Endocrinology, Pharmacology and Toxicology, and Blood Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
8
Department of Pathology & Immunology, Washington University, St Louis, MO 63110, USA. Electronic address: gjrandolph@wustl.edu.

Abstract

Lipoproteins trapped in arteries drive atherosclerosis. Extravascular low-density lipoprotein undergoes receptor uptake, whereas high-density lipoprotein (HDL) interacts with cells to acquire cholesterol and then recirculates to plasma. We developed photoactivatable apoA-I to understand how HDL passage through tissue is regulated. We focused on skin and arteries of healthy mice versus those with psoriasis, which carries cardiovascular risk in man. Our findings suggest that psoriasis-affected skin lesions program interleukin-17-producing T cells in draining lymph nodes to home to distal skin and later to arteries. There, these cells mediate thickening of the collagenous matrix, such that larger molecules including lipoproteins become entrapped. HDL transit was rescued by depleting CD4+ T cells, neutralizing interleukin-17, or inhibiting lysyl oxidase that crosslinks collagen. Experimental psoriasis also increased vascular stiffness and atherosclerosis via this common pathway. Thus, interleukin-17 can reduce lipoprotein trafficking and increase vascular stiffness by, at least in part, remodeling collagen.

KEYWORDS:

Th17 immunity; artery; atherosclerosis; autoimmunity; collagen; cytokines; extracellular matrix; fibrosis; interstitial transport; skin

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