Atheroprotective Immunity and Interleukin-10 Linked to Reduced Characteristics of Plaque Stability

[Display omitted] •Ongoing development of immunotherapies for cardiovascular disease aims to boost atheroprotective responses.•Studying the long-term implications of atheroprotective immunity in mice revealed 2 distinct pathways.•The IL-10 pathway was associated with characteristics of reduced plaqu...

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Published in:JACC-BASIC TO TRANSLATIONAL SCIENCE Vol. 10; no. 8; p. 101322
Main Authors: Yu, Yinda, Lin, Shiying, Pan, Yueyun, He, Ning, Wu, Yanzhao, Ahmed, Osman, Hedin, Ulf, Karlsson, Mikael C.I., Li, Nailin, Gisterå, Anton
Format: Journal Article Publication
Language:English
Published: United States Elsevier Inc 01.08.2025
Elsevier
Subjects:
adaptive immunity
apolipoprotein B-100
atherosclerosis
Cardiovascular
cardiovascular disease
LDL
lipoproteins
Original Research - Preclinical
T-lymphocyte
atherosclerosis
cardiovascular disease
TCR
IL
Treg
adaptive immunity
apoB
BT
Tr1
apolipoprotein B-100
Th
LDL
HuBL
T-lymphocyte
lipoproteins
human APOB100-transgenic Ldlr −/ − mice
regulatory T cell
low-density lipoprotein
T-cell receptor
type 1 regulatory T cell
T-helper
interleukin
apolipoprotein B
apolipoprotein B–reactive T cell
ISSN:2452-302X, 2452-302X
Online Access:Get full text
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Summary:[Display omitted] •Ongoing development of immunotherapies for cardiovascular disease aims to boost atheroprotective responses.•Studying the long-term implications of atheroprotective immunity in mice revealed 2 distinct pathways.•The IL-10 pathway was associated with characteristics of reduced plaque stability and increased recurrent cardiovascular events in humans.•Further research should explore ways to enhance atheroprotective pathways without compromising plaque stability. Autoimmunity to low-density lipoprotein (LDL) is linked to atherosclerosis, with LDL immunization proposed as a preventive measure, but the mechanisms of atheroprotective immunity are not well understood. We investigated T-cell responses to LDL using 2 T-cell receptor transgenic mouse strains. At 52 weeks, BT1×HuBL mice showed reduced atherosclerosis, increased humoral responses against LDL, and lower plasma cholesterol. Conversely, BT3×HuBL mice had reduced atherosclerosis without changes in cholesterol, linked to increased type 1 regulatory T cells, interleukin (IL)-10 production, and decreased characteristics of plaque stability. In human plaques, IL10 mRNA negatively correlated with collagen content, and IL-10 inhibited collagen production in vitro. We conclude that atheroprotective LDL immunity elicits 2 distinct pathways: lipid-lowering immune responses and local anti-inflammatory IL-10 production. Because IL-10 is associated with decreased plaque stability and increased risk of cardiovascular events, treatments aimed at promoting IL-10 signaling over extended periods to reduce vascular inflammation should be carefully monitored.
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ISSN:2452-302X
2452-302X
DOI:10.1016/j.jacbts.2025.101322