Diisodecyl phthalate aggravates thyroid autoimmune injury in thyroglobulin-sensitized rats via endoplasmic reticulum stress-mediated apoptosis and Th17/Treg dysregulation.

To clarify the effects and mechanisms of diisodecyl phthalate (DIDP) in autoimmune thyroiditis, this study established a thyroglobulin (TG)-induced autoimmune thyroiditis model in female Wistar rats. DIDP (0.15, 1.5, or 15 mg/kg/day) was administered to rats via gavage were administered to rats via gavage, an inhibitor of endoplasmic reticulum stress (ERS) was used for intervention, Thyroid histopathology, serum thyroid-related antibodies and hormones, as well as ERS-associated proteins and Th17/Treg immune balance markers were evaluated. TG administration induced typical AITD-like features, including thyroid inflammatory infiltration, follicular damage, increased serum TgAb and FT4 levels, and decreased FT3 levels, accompanied by mild ERS activation and Th17/Treg imbalance. DIDP co-exposure further aggravated TG-induced thyroid inflammation and structural damage by enhancing ERS activation and disrupting Th17/Treg immune homeostasis, resulting in increased TgAb and FT4 levels and reduced FT3 concentration. These effects were significantly alleviated by 4-PBA intervention. In conclusion, DIDP aggravates thyroid autoimmune injury in TG-sensitized model by activating ERS and impairing Th17/Treg immune regulation.