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Interleukin-17 Drives Interstitial Entrapment of Tissue Lipoproteins in Experimental Psoriasis. Cell Metab 2019 Feb 05;29(2):475-487.e7

Date

11/13/2018

Pubmed ID

30415924

Pubmed Central ID

PMC6365189

DOI

10.1016/j.cmet.2018.10.006

Scopus ID

2-s2.0-85060717940 (requires institutional sign-in at Scopus site)   36 Citations

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.

Author List

Huang LH, Zinselmeyer BH, Chang CH, Saunders BT, Elvington A, Baba O, Broekelmann TJ, Qi L, Rueve JS, Swartz MA, Kim BS, Mecham RP, Wiig H, Thomas MJ, Sorci-Thomas MG, Randolph GJ

Authors

Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of Wisconsin
Michael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

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