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Publications

Journal Article Ppublish

PubMed: 40674844 DOI: 10.1016/j.jacbts.2025.101322

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

JACC Basic Transl Sci 10(8):101322

Authors: Yinda Yu, Shiying Lin, Yueyun Pan, Ning He, Yanzhao Wu, Osman Ahmed, Ulf Hedin, Mikael C I Karlsson, Nailin Li, Anton Gisterå

Affiliations

  • Department of Medicine Solna, Karolinska Institutet, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
  • Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
  • Department of Medicine Solna, Karolinska Institutet, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.
  • Department of Medicine Solna, Karolinska Institutet, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain.
  • Department of Molecular Medicine and Surgery, Department of Vascular Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
  • Department of Medicine Solna, Karolinska Institutet, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.

Abstract

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.

MeSH

Cells, Lipoproteins, Cardiovascular Diseases, Collagen, Adaptive Immunity, Cholesterol, Immunity, Atherosclerosis, Interleukin-10