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This review systematically summarizes the dynamic immune microenvironment in atherosclerosis, moving beyond static cell categorization to explicitly link immune heterogeneity to the major stages of disease progression: lesion initiation, necrotic core expansion, fibrous cap weakening, and thrombotic complications. We further describe the continuous phenotypic shifts of key immune populations, particularly the transition of macrophages into specialized lipid-handling states and the context-dependent roles of distinct T-cell, B-cell, and innate immune cell subsets. By integrating recent advances in single-cell transcriptomics, we highlight how local molecular networks, cellular crosstalk, and impaired clearance of apoptotic cells govern plaque vulnerability. Furthermore, we critically evaluate spatiotemporal variations across vascular territories and the complex clinical implications of immune checkpoint regulation. Finally, this review discusses current barriers to clinical translation and explores the therapeutic potential of precision immunomodulatory strategies, aiming to bridge the gap between basic immunological mechanisms and targeted cardiovascular therapies.<\/jats:p>","DOI":"10.31083\/rcm49094","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:17:46Z","timestamp":1788437866000},"source":"Crossref","is-referenced-by-count":0,"title":["Functional Heterogeneity of Immune Cell Subpopulations in Atherosclerosis: From Basic Mechanisms to Precision Therapy"],"prefix":"10.31083","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6002-1145","authenticated-orcid":true,"given":"Ming","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiology, Zibo Central Hospital Affiliated to Shandong Medical and Pharmaceutical University, 255036 Zibo, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ce","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zibo Central Hospital, 255036 Zibo, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9125-3024","authenticated-orcid":true,"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zibo Central Hospital, 255036 Zibo, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Roy P, Orecchioni M, Ley K. 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