ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
This article is part of the Research TopicMacrophages at the Crossroads of Fibrosis and ImmunosuppressionView all 3 articles
TMEM106A Mediates Atherosclerosis Progression Through Macrophage-Centered Immune Responses and Chemokine Signaling
Provisionally accepted
- 1Weifang People's Hospital, Weifang, China
- 2Heze Municipal Hospital, Heze, China
- 3The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
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Background: Atherosclerosis (AS) remains a leading cause of cardiovascular morbidity and mortality, characterized by intricate interactions between immune dysregulation and lipid metabolism abnormalities—identifying key mediators in its pathogenesis is critical for improving diagnostics and therapies. This study focuses on Transmembrane Protein 106A (TMEM106A) to clarify its role and clinical relevance in AS progression. Methods: Public transcriptomic datasets (GSE43292, GSE100927, GSE28829) were analyzed to assess TMEM106A expression and diagnostic value; single-cell RNA-seq data (GSE159677) defined its cellular localization. Immune infiltration (ssGSEA, Cibersort, xCell) and CellChat (intercellular communication) analyses explored its immune associations. In vivo validation used high-fat diet-induced AS in ApoE⁻/⁻ mice, and in vitro experiments with RAW264.7 macrophages included TMEM106A silencing to test functional effects. Results: TMEM106A was significantly upregulated in AS samples across datasets, with strong diagnostic efficacy (AUC 0.80–0.95). Single-cell analysis confirmed its specific enrichment in macrophages, with functional links to immune-related pathways. TMEM106A promoted macrophage infiltration, foam cell formation, oxidative stress, and inflammatory responses, while regulating PLCB2 in chemokine signaling; silencing TMEM106A alleviated these pro-atherosclerotic effects. Conclusion: TMEM106A contributes to AS progression by modulating macrophage-mediated immune responses and chemokine signaling, as validated in experimental models. These findings support its potential as a clinically relevant biomarker and promising therapeutic target for AS intervention.
Keywords: Atherosclerosis, TMEM106a, Macrophages, Chemokine signaling pathway, plcB2
Received: 07 Aug 2025; Accepted: 25 Nov 2025.
Copyright: © 2025 Gao, Li, Liu, Fang, Lun, Zhang, Zhao and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhenhua Li
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