Journal: Frontiers in Immunology

Article Title: HMGB1 dysregulation: a neuroimmune bridge to cognitive impairment in autoimmune thyroiditis

doi: 10.3389/fimmu.2026.1764288

Figure Lengend Snippet: CD4 + T cells and IL-17A infiltration and protein expression in hippocampus, cortex, and thyroid. IF staining of hippocampus (A) and cortex (B) showing CD4 (green), IL-17A (red), DAPI (blue), and merged signals. Quantification of co-localized CD4 + T cells and IL-17A in hippocampus (C) and cortex (D) . Western blot analysis of IL-17A, Hmgb1 and RAGE protein levels in hippocampus and cortex (n = 3 mice) (E) . IF staining of thyroid showing CD4 (green), IL-17A (red), DAPI (blue), and merged signals (F) . Quantification of co-localized CD4 + T cells and IL-17A in thyroid (n = 3 mice) (G) . Data are presented as mean ± SD. *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001 (n = 6 mice).

Article Snippet: Membranes were blocked with 5% non-fat milk in TBST for 2 h, then incubated overnight at 4 °C with primary antibodies against Hmgb1 (Abcam, ab190377), IL-17A (Abcam, ab79056), and RAGE (Cell Signaling Technology, 42544; all 1:1000), with GAPDH as loading control.

Techniques: Expressing, Staining, Western Blot

Journal: Frontiers in Immunology

Article Title: HMGB1 dysregulation: a neuroimmune bridge to cognitive impairment in autoimmune thyroiditis

doi: 10.3389/fimmu.2026.1764288

Figure Lengend Snippet: Here we propose a mechanistic model linking experimental autoimmune thyroiditis (EAT) to neuroinflammation and cognitive deficits. EAT triggers peripheral immune activation, characterized by elevated levels of thyroglobulin antibodies (TgAb) and recruitment of CD4 + T cells. TgAb and infiltrating CD4 + T cells cross the blood–brain barrier (BBB) and enter the brain, where they activate microglia and astrocytes. Activated glial cells release extracellular high-mobility group box 1 (HMGB1), which further stimulates CD4 + T-cell activation via the receptor for advanced glycation end products (RAGE), leading to increased IL-17A production. IL-17A, in turn, amplifies microglial and astrocytic activation and upregulates pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. This cascade exacerbates neuroinflammation and ultimately contributes to cognitive impairment. Key: TgAb (red dots), HMGB1 (purple dots), CD4 + T cells (cyan circles), IL-17A (cyan small dots), astrocytes (green), microglia (orange); solid arrows indicate promoting effects. Created in BioRender. Q, Q. (2026) https://BioRender.com/6ff1fxp .

Article Snippet: Membranes were blocked with 5% non-fat milk in TBST for 2 h, then incubated overnight at 4 °C with primary antibodies against Hmgb1 (Abcam, ab190377), IL-17A (Abcam, ab79056), and RAGE (Cell Signaling Technology, 42544; all 1:1000), with GAPDH as loading control.

Techniques: Activation Assay