{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T00:54:24Z","timestamp":1794012864489,"version":"4.8.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>This study explored the role of tryptophan (Trp) metabolism in Hashimoto\u2019s thyroiditis (HT) pathogenesis using clinical samples and animal models, given the unclear mechanisms and limited treatments of HT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinically, serum Trp, lactic acid, and alanine levels in 10 HT patients and 10 healthy controls were measured by ELISA. In animal experiments, female C57BL\/6 mice were divided into Con, HT, HT+T (Trp supplemented), and HT+I (Trp metabolism inhibitor IDO1\/TDO-IN-4 treated) groups. After inducing autoimmune thyroiditis, various tests were conducted, including ELISA for inflammation factors, HE staining for thyroid pathology, flow cytometry for T cell subsets, RNA-seq for gene expression, Western Blotting for PI3K-Akt pathway proteins, and CIBERSORT for immune cell analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HT patients had significantly lower serum Trp levels. The HT group showed thyroid damage and increased inflammation factors. Trp supplementation alleviated thyroid damage and reduced inflammation factors, while the inhibitor worsened them. Trp also regulated T cell subsets and immune cell environment. RNA-seq and Western Blotting indicated Trp\u2019s impact on immune response and PI3K-Akt pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Trp metabolism abnormality is associated with HT. Trp supplementation can alleviate HT progression by regulating T cell function and the PI3K-Akt pathway, while inhibiting Trp metabolism exacerbates it. This suggests Trp metabolism\u2019s potential as a therapeutic target for HT.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1605739","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T05:33:46Z","timestamp":1756791226000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Dysregulated tryptophan metabolism: driving T cell subsets and PI3K-Akt pathway alterations in Hashimoto\u2019s thyroiditis"],"prefix":"10.3389","volume":"16","author":[{"given":"Lijian","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingwei","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxi","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7326\/M23-1593","article-title":"Thyroidectomy for euthyroid patients with hashimoto disease and persisting symptoms","volume":"177","author":"Hoff","year":"2024","journal-title":"Ann Intern Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"27902","DOI":"10.1038\/s41598-024-78938-7","article-title":"Thyroid antibodies in Hashimoto\u2019s thyroiditis patients are positively associated with inflammation and multiple symptoms","volume":"14","author":"Li","year":"2024","journal-title":"Sci Rep"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.879824","article-title":"A global regulatory network for dysregulated gene expression and abnormal metabolic signaling in immune cells in the microenvironment of graves\u2019 Disease and hashimoto\u2019s thyroiditis","volume":"13","author":"Zheng","year":"2022","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.06.004","article-title":"Tryptophan metabolism in health and disease","volume":"35","author":"Xue","year":"2023","journal-title":"Cell Metab"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-01028-7","article-title":"Immune regulation through tryptophan metabolism","volume":"55","author":"Seo","year":"2023","journal-title":"Exp Mol Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3380","DOI":"10.3390\/nu16193380","article-title":"Tryptophan metabolism disorder-triggered diseases, mechanisms, and therapeutic strategies: A scientometric review","volume":"16","author":"Chen","year":"2024","journal-title":"Nutrients"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2023.04.006","article-title":"Modulation of T cells by tryptophan metabolites in the kynurenine pathway","volume":"44","author":"Stone","year":"2023","journal-title":"Trends Pharmacol Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1273","article-title":"Plasmacytoid dendritic cells in patients with autoimmune thyroid disease","volume":"98","author":"Leskela","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.18295\/squmj.2016.17.02.007","article-title":"Imbalances in T cell-related transcription factors among patients with hashimoto\u2019s thyroiditis","volume":"17","author":"Safdari","year":"2017","journal-title":"Sultan Qaboos Univ Med J"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2019.01.003","article-title":"Immunological aspects of autoimmune thyroid disease - 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