Bisnauthsing, H.; Chu, W. K.

Background: Thyroid Eye Disease (TED) is an autoimmune orbital disorder driven by pathogenic T cell subsets, including T-helper 1 (Th1) and follicular helper T (Tfh) cells, which sustain orbital inflammation and thyroid-stimulating immunoglobulin (TSI) production. Selenium supplementation has demonstrated clinical benefit in mild TED, yet its immunological mechanisms remain poorly defined. Methods: A murine TED model was established in female BALB/c mice via TSHR plasmid immunisation. Animals maintained on a low-selenium diet (0.07 ppm) received sodium selenite supplementation at 0.2 mg/kg/day. Orbital pathology was assessed by immunohistochemistry, H&E and Masson's Trichrome staining. T cell subset abundance was quantified by flow cytometry, and serum T4, TRAb, and IL 21 levels were measured by ELISA. In vitro dose-response experiments examined the effects of selenium on Tfh cell viability, IL-21 production, apoptosis, and ferroptosis. Results: Selenium supplementation reduced CD3; Tcell orbital infiltration, collagen fibrosis, and serum T4 and TRAb levels in TSHR-immunised mice. Flow cytometry revealed significant reductions in Tfh and Th1 cell abundance, with Th17 cells unaffected. Serum IL21 and B-cell abundance were also markedly reduced in vivo. In vitro, selenium exhibited a biphasic, dose-dependent effect on Tfh cells: low concentrations maintained viability and IL 21 production, while higher concentrations induced ferroptosis and apoptosis. Conclusions: Selenium modulates pathogenic T cell responses in TED, most prominently suppressing the Tfh compartment and attenuating the Tfh B cell autoantibody axis via ferroptosis and apoptosis. These findings suggest a mechanistic framework for the clinical benefit of selenium in mild TED and highlight the importance of dose selection within its narrow therapeutic window.