{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:28:32Z","timestamp":1792124912278,"version":"4.4.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Cognitive and affective disturbances are frequent extra-thyroidal manifestations of Hashimoto\u2019s thyroiditis (HT), even in euthyroid patients, with severe cases progressing to Hashimoto\u2019s encephalopathy. The mechanisms underlying these CNS complications are still unclear; however, neuroinflammation\u2014driven by CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells and Hmgb1-mediated glial activation\u2014is increasingly implicated. To elucidate this link, we explore in an experimental autoimmune thyroiditis (EAT) model whether Hmgb1 amplifies immune pathways to exacerbate cognitive and emotional impairments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In C57BL\/6 mice, EAT was induced by multiple injections of pTg. Histopathological analysis and ELISA confirmed the induction of thyroiditis. Exploratory behavior was assessed in an open field test, and associative memory was evaluated using the novel object recognition task, Y-maze, and Morris water maze. PCR was performed to detect inflammatory markers indicative of neuroinflammation. Furthermore, Western blotting was used to assess Hmgb1 release, and immunofluorescence (IF) was employed to examine the cytoplasmic translocation of Hmgb1 in brain sections, as well as the morphology and activation markers of microglia and astrocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mice with EAT, despite preserved systemic thyroid hormone levels, displayed significant deficits in both spatial and recognition memory. Histological and immunofluorescence analyses revealed pronounced activation of microglia in the cortex and hippocampus, accompanied by an increased number of A1-like astrocytes and disrupted polarization of AQP4. Infiltrating CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells were detected in these regions and were found to secrete IL-17A. Neuroinflammatory changes were associated with elevated Hmgb1 expression and increased numbers of CD68\n                      <jats:sup>+<\/jats:sup>\n                      microglia, as confirmed by co-localization analyses. Pharmacological inhibition of Hmgb1 markedly reduced microglial activation and alleviated cognitive impairments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results identify Hmgb1 as a key factor that translates peripheral thyroid autoimmunity into central neuroinflammation. It functions as a driving force behind pathogenic glial and Th17\/IL-17A responses, which propagate neurotoxicity and lead to cognitive-affective dysfunction. Targeting Hmgb1 may thus offer a viable therapeutic approach to prevent or treat neurological symptoms associated with HT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1764288","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T06:33:26Z","timestamp":1771310006000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["HMGB1 dysregulation: a neuroimmune bridge to cognitive impairment in autoimmune thyroiditis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jue","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Binzhou Medical University Hospital","place":["Binzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoping","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Binzhou Medical University Hospital","place":["Binzhou, 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