Interleukin-17 Drives Interstitial Entrapment of Tissue Lipoproteins in Experimental Psoriasis. Cell Metab 2019 Feb 05;29(2):475-487.e7
Date
11/13/2018Pubmed ID
30415924Pubmed Central ID
PMC6365189DOI
10.1016/j.cmet.2018.10.006Scopus ID
2-s2.0-85060717940 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
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 GJAuthors
Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of WisconsinMichael 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
AnimalsApolipoprotein 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