TSG6 Plays a Role in Improving Orbital Inflammatory Infiltration and Extracellular Matrix Accumulation in TAO Model Mice.

Abstract

TSG-6 plays a wide anti-inflammatory and therapeutic role in a variety of autoimmune diseases as the key mediator of mesenchymal stem cells (MSCs). We aimed to test whether TSG-6 could exert similar effects as MSCS in TAO via establishing TAO animal model immunized by hTSHR-A subunit plasmid. We tested the expression level of TSG-6 on intraconal orbital fat from controls and patients with TAO. We established a stable thyroid-associated ophthalmopathy animal model by immunizing 6-week-old female Balb/c mice with recombination hTSHR-A subunit plasmid. After four immunizations, TSG-6 or dexamethasone was injected through the tail vein. The effects of the drugs on body weight, thyroid function, orbital inflammation, fibrosis and lipogenesis were observed. The expression of TSG-6 in the orbital tissues of TAO patient is lower than that of normal people. In our animal model, mice showed weight loss, higher TT4 and TSHR antibody levels, and ocular symptoms such as inflammation and proptosis. TSG-6 can reduce ocular fibrosis and lipogenesis by inhibiting the infiltration of CD3+ T lymphocytes and macrophages in the mouse model of thyroid associated ophthalmopathy. Compared with dexamethasone, TSG-6 showed comparable anti-inflammatory effect, moreover, it has given a better performance in inhibiting adipogenesis. It was demonstrated that TSG-6 has a considerable positive impact on improving eye symptoms of TAO mice, which could be a novel candidatefortheearly treatment of TAO.