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

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.

• Authors: Li-Hao Huang, Bernd H Zinselmeyer, Chih-Hao Chang, Brian T Saunders, Andrew Elvington, Osamu Baba, Thomas J Broekelmann, Lina Qi, Joseph S Rueve, Melody A Swartz, Brian S Kim, Robert P Mecham, Helge Wiig, Michael J Thomas, Mary G Sorci-Thomas, Gwendalyn J Randolph
• Journal: Cell metabolism (Cell Metab) Vol. 29 Issue 2 Pg. 475-487.e7 (02 05 2019) ISSN: 1932-7420 [Electronic] United States
• PMID: 30415924 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Apolipoprotein A-I
• Interleukin-17
• Lipoproteins, HDL
• Protein-Lysine 6-Oxidase

Topics

• Animals
• Apolipoprotein A-I (metabolism)
• Atherosclerosis (metabolism)
• Biological Transport
• CD4-Positive T-Lymphocytes (cytology, metabolism)
• Disease Models, Animal
• HEK293 Cells
• Humans
• Interleukin-17 (metabolism)
• Lipoproteins, HDL (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Protein-Lysine 6-Oxidase (metabolism)
• Psoriasis (metabolism)
• Skin (metabolism, pathology)