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

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. Cell Metabolism, Volume 29, Issue 2, 5 February 2019, Pages 475-487.e7 Read More

Abstract

HDL removes tissue cholesterol and recirculates to the plasma. Huang et al. generated a photoactivatable HDL tracking tool that they applied to psoriasis, which has been clinically linked to cardiovascular comorbidity. They find that Th17 autoimmunity promotes collagen deposition in skin and arteries, thus entrapping HDL and LDL to drive cardiovascular risk. © 2018 Elsevier Inc.

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. © 2018 Elsevier Inc.

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Posted on February 12, 2019
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