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The differentiation of CD4<jats:sup>+<\/jats:sup>T cell subsets in patients with HT is imbalanced, with Treg cells decreased and Th17 cells abnormally activated. Fatty acid oxidation supports the differentiation of Th17 cells and induces inflammation, but the specific mechanism is still unknown. This study aimed to explore the role of fatty acid oxidation and its pathway in the pathogenesis of autoimmune thyroiditis and the immune mechanism.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In in vitro experiments, a total of 60 HT patients and 20 healthy controls were selected and their CD4<jats:sup>+<\/jats:sup>T cells were sorted by magnetic beads. All 80 samples were divided into 4 groups on average: HC group (Healthy control group), HT group (Hashimoto thyroiditis CD4<jats:sup>+<\/jats:sup>T cell inactive group), TCC group(Hashimoto thyroiditis CD4<jats:sup>+<\/jats:sup>T cell activation), TCC + ETO group(Hashimoto thyroiditis CD4<jats:sup>+<\/jats:sup>T cell activation + Etomoxir group). In in vivo experiments, the mice were randomly divided into 3 groups: Con group(Control group), mTg group (CBA\/J mice were injected with mTg for modeling, that is EAT mice group), and mTg + ETO group (Etomoxir intervention in EAT mice group). Fatty acid oxidation substrates of CD4<jats:sup>+<\/jats:sup>T cells in human peripheral blood were detected by targeted metabolomics. The expressions of key fatty acid oxidation proteins mTOR, ACC1 and CPT1A were detected by Western blotting. The proportion of CD4<jats:sup>+<\/jats:sup>T cell subtype differentiation in human and mouse models was detected by flow cytometry. The severity of EAT was detected by HE staining.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Compared with healthy controls, the level of CPT1A in CD4<jats:sup>+<\/jats:sup>T cells of HT patients was increased, and the intracellular fatty acid content was significantly decreased, indicating that the level of fatty acid oxidation was enhanced in HT patients. After adding Etomoxir, the level of fatty acid oxidation was significantly inhibited, and the imbalance of CD4<jats:sup>+<\/jats:sup>T cell subpopulation differentiation in HT patients was reversed. In EAT mice, the mTOR\/ACC1\/CPT1A pathway was significantly activated, and its expression level was decreased after adding Etomoxir. At the same time, Etomoxir could reverse the reprogramming of abnormal metabolism in EAT mice cells, reduce the spleen index, and improve lymphocyte infiltration in the thyroid.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The mTOR\/ACC1\/CPT1A fatty acid oxidation pathway of CD4<jats:sup>+<\/jats:sup>T cells in Hashimoto\u2019s thyroiditis was increased, and treatment with Etomoxir could inhibit the activation of this pathway, and reverse the reprogramming of abnormal metabolism in CD4<jats:sup>+<\/jats:sup>T cells, thereby reducing Hashimoto\u2019s thyroiditis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s40618-024-02501-4","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T06:53:47Z","timestamp":1733468027000},"page":"845-859","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The immune mechanism of the mTOR\/ACC1\/CPT1A fatty acid oxidation signaling pathway in Hashimoto\u2019s thyroiditis"],"prefix":"10.1007","volume":"48","author":[{"given":"Lu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingjie","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0529-0428","authenticated-orcid":false,"given":"Haixia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"issue":"10","key":"2501_CR1","doi-asserted-by":"publisher","first-page":"102649","DOI":"10.1016\/j.autrev.2020.102649","volume":"19","author":"M RALLI","year":"2020","unstructured":"RALLI M, ANGELETTI D, FIORE M et al (2020) Hashimoto\u2019s thyroiditis: an update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation.[J\/OL]. 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The clinical study was approved by the Ethics Committee of the Second Affiliated Hospital of Dalian Medical University (Ethics Approval Number: 2023 NO.218); the animal study was approved by the Medical Ethics Committee of Dalian Medical University (Ethics Approval Number: AEE22092).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants and\/or animals"}},{"value":"No informed consent is required.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}