{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:03:33Z","timestamp":1792803813299,"version":"4.5.0"},"reference-count":206,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cardiovascular Research Fund"},{"name":"Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care","id":[{"id":"https:\/\/ror.org\/043s0fn12","id-type":"ROR","asserted-by":"crossref"}]},{"name":"ONO Medical Research Foundation","id":[{"id":"https:\/\/ror.org\/00krdxg91","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Nihon University Research Grant-in-aid for Early-Career Scientists","id":[{"id":"https:\/\/ror.org\/05jk51a88","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Nihon University Research Grant","id":[{"id":"https:\/\/ror.org\/05jk51a88","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Hypercholesterolemia causes atherosclerosis by inducing immune cell migration and chronic inflammation in arterial walls. Recent single-cell analyses reveal the presence of lipid-enriched foamy macrophages, as well as other macrophage subtypes, neutrophils, T cells, and B cells, in atherosclerotic plaques in both animal models and humans. These cells interact with each other and other cells, including non-immune cells such as endothelial cells and smooth muscle cells. They thereby regulate metabolic, inflammatory, phagocytic, and cell death processes, thus affecting the progression and stability of atherosclerotic plaques. The nuclear receptors liver X receptor (LXR)\u03b1 and LXR\u03b2 are transcription factors that are activated by oxysterols and regulate lipid metabolism and immune responses. LXRs regulate cholesterol homeostasis by controlling cholesterol\u2019s transport, absorption, synthesis, and breakdown in the liver and intestine. LXRs are also highly expressed in tissue-resident and monocyte-derived macrophages and other immune cells, including both myeloid cells and lymphocytes, and they regulate both innate and adaptive immune responses. Interestingly, LXRs have immunosuppressive and immunoregulatory functions that are cell-type-dependent. In animal models of atherosclerosis, LXRs have been shown to be involved in both progression and regression phases. The pharmacological activation of LXR enhances cholesterol efflux from macrophages and promotes atherosclerosis progression. Deleting LXR in immune cells, especially myeloid cells, accelerates atherosclerosis by increasing monocyte migration, macrophage proliferation and activation, and neutrophil extracellular traps (NETs); furthermore, the deletion of hematopoietic LXRs impairs the regression of atherosclerotic plaques. Therefore, LXRs in immune cells may be a potent therapeutic target for atherosclerosis.<\/jats:p>","DOI":"10.3390\/biom15040579","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T09:06:51Z","timestamp":1744621611000},"page":"579","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Exploring the Roles of Liver X Receptors in Lipid Metabolism and Immunity in Atherosclerosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4012-4353","authenticated-orcid":false,"given":"Kaori","family":"Endo-Umeda","sequence":"first","affiliation":[{"name":"Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4630-905X","authenticated-orcid":false,"given":"Makoto","family":"Makishima","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/s41569-023-00883-1","article-title":"Flow-induced reprogramming of endothelial cells in atherosclerosis","volume":"20","author":"Tamargo","year":"2023","journal-title":"Nat. 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