Inhibition of IL-17A Attenuates Atherosclerotic Lesion Development in ApoE-Deficient Mice

Abstract

Material

The C-terminal module IV of connective tissue growth factor is a novel immune modulator of the Th17 response

“…CCN2 has been involved in several chronic diseases, including skin disorders, cardiac hypertrophy, atherosclerosis, pulmonary hypertension, and lung and liver diseases, 12 where IL-17A is a key player. 32,33,[55][56][57][58] In the nonimmune murine model of UUO, we have observed elevated renal levels of IL-17A and infiltrating inflammatory cells associated with renal CCN2 overexpression. Although future studies are needed, our data showing that IL-17A blockade ameliorated CCN2-induced renal inflammation support the concept of CCN2 module IV regulates IL17A production R Rodrigues-Díez et al IL-17A-neutralizing antibody as a promising tool for chronic inflammatory diseases, including chronic kidney diseases.…”

“…54 Several IL-17A blockade strategies, including neutralizing antibodies or receptor gene targeting, ameliorated several experimental nonimmune diseases. [32][33][34][35][36] Preliminary data in rheumatoid arthritis and uveitis, 34 and more recently, data from two phase 2 clinical trials, in which patients with psoriasis were treated with specific targeting antibodies for IL-17A or its receptor, 35,36 have shown beneficial effects in humans. CCN2 has been involved in several chronic diseases, including skin disorders, cardiac hypertrophy, atherosclerosis, pulmonary hypertension, and lung and liver diseases, 12 where IL-17A is a key player.…”

“…30,31 Growing evidence suggests that IL-17A, the Th17 effector cytokine, besides participating in immunemediated diseases, is also involved in chronic inflammatory diseases such as atherosclerosis, and hypertension. [30][31][32][33] Recent studies suggest that blockade of IL-17A is a promising tool for chronic human inflammatory diseases, as observed in rheumatoid arthritis, uveitis, and psoriasis. [34][35][36] Our aim was to explore whether the CCN2(IV) could regulate the Th17 response and therefore contribute to persistent inflammation.…”

Aortic VCAM‐1: an early marker of vascular inflammation in collagen‐induced arthritis

“…Moreover, its role in vascular dysfunction such as atherosclerosis is controversial 45, 46, 47. According to Madhur et al ., IL‐17A is necessary to induce superoxide vascular production in response to a high fat diet in ApoE −/− mice 48.…”

Emerging biomarkers and intervention targets for immune-modulation of atherosclerosis – A review of the experimental evidence

“…The role of Th17 in atherosclerosis is also debated as conflicting reports exist (30)(31)(32). In contrast to CD4 + T helper cells, CD8 + cytolytic T lymphocytes have not been extensively studied, even though CD8 + T cells are abundant in atherosclerotic plaques and they have been shown to be activated in hypercholesterolemic Apoe -/-mice (33).…”