{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:05:06Z","timestamp":1785870306245,"version":"3.56.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017695","name":"Health Commission of Hunan Province","doi-asserted-by":"publisher","award":["D202317018022"],"award-info":[{"award-number":["D202317018022"]}],"id":[{"id":"10.13039\/100017695","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009377","name":"Education Department of Hunan Province","doi-asserted-by":"publisher","award":["17C1477"],"award-info":[{"award-number":["17C1477"]}],"id":[{"id":"10.13039\/100009377","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Parkinson\u2019s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss and neuroinflammation, with emerging roles of peripheral immune dysregulation in disease progression. This study aimed to investigate the regulatory network of CD4\u2009+\u2009T cells in PD through multi-omics integrative analysis. Transcriptomic and miRNA datasets from peripheral blood mononuclear cells (PBMCs) of 20 PD patients and 17 healthy controls were analyzed (GSE22491, GSE100054, GSE16658). Differential expression analysis identified 287 mRNAs and 73 miRNAs (|log\u2082(fold change)|\u2009\u2265\u20090.5, false discovery rate &lt;0.05), with 25 immune-related mRNAs selected for further analysis. Machine learning (LASSO regression and SVM-RFE) prioritized seven hub genes, including\n                    <jats:italic>CD4<\/jats:italic>\n                    and\n                    <jats:italic>SEMA6A<\/jats:italic>\n                    . A competing endogenous RNA (ceRNA) network was constructed, comprising 38 lncRNAs, three miRNAs (miR-155-5p, miR-27a-3p, miR-27b-3p), and their target mRNAs\n                    <jats:italic>CD4<\/jats:italic>\n                    and\n                    <jats:italic>SEMA6A<\/jats:italic>\n                    . Four lncRNAs (including\n                    <jats:italic>XIST, NORAD<\/jats:italic>\n                    , and\n                    <jats:italic>INE1<\/jats:italic>\n                    ) were identified to functionally regulate\n                    <jats:italic>CD4<\/jats:italic>\n                    . Immune cell infiltration analysis revealed increased proportions of na\u00efve CD4\u2009+\u2009T cells and activated dendritic cells in PD patients.\n                    <jats:italic>CD4<\/jats:italic>\n                    expression positively correlated with \u03b3\u03b4 T cells (r\u2009=\u20090.48, p\u2009=\u20090.032) and activated NK cells (r\u2009=\u20090.45, p\u2009=\u20090.048). Gene set enrichment analysis associated\n                    <jats:italic>CD4<\/jats:italic>\n                    with neurodegenerative pathways (e.g., Parkinson\u2019s disease: normalized enrichment score\u2009=\u20091.57,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.002) and oxidative phosphorylation (normalized enrichment score\u2009=\u20091.89,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20097.4\u2009\u00d7\u200910\u2009\u207b\u2009\u2076). These findings highlight a peripheral CD4\u2009+\u2009T cell-centric ceRNA network that modulates immune-metabolic crosstalk and neuroinflammation in PD. This study provides novel insights into immune-driven neurodegeneration and suggests potential therapeutic targets for PD through metabolic-immune reprogramming.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0337808","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T18:30:15Z","timestamp":1764700215000},"page":"e0337808","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["ceRNA regulatory network and immune-neurodegenerative mechanisms of peripheral CD4+ T cells in parkinson\u2019s disease"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0227-415X","authenticated-orcid":true,"given":"Lijun","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"issue":"8","key":"pone.0337808.ref001","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1136\/jnnp-2019-322338","article-title":"Parkinson\u2019s disease: etiopathogenesis and treatment","volume":"91","author":"J Jankovic","year":"2020","journal-title":"J Neurol Neurosurg 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